Inflammasomes
Caspase 1
Interleukin-1beta
Nod Signaling Adaptor Proteins
Interleukin-18
CARD Signaling Adaptor Proteins
Cryopyrin-Associated Periodic Syndromes
Hereditary Autoinflammatory Diseases
Carrier Proteins
Receptors, Pattern Recognition
Apoptosis Regulatory Proteins
Neuronal Apoptosis-Inhibitory Protein
Inflammation
Calcium-Binding Proteins
Immunity, Innate
Cytoskeletal Proteins
Macrophages
Bacterial Secretion Systems
Flagellin
Signal Transduction
Legionella pneumophila
Multiprotein Complexes
Adaptor Proteins, Signal Transducing
Mice, Knockout
Nuclear Proteins
Mice, Inbred C57BL
Cell Death
Models, Immunological
Inflammation Mediators
Cathepsin B
Autoimmunity
Host-Pathogen Interactions
Autophagy
Caspases
Enzyme Activation
Cytokines
Inflammation, oxidative stress and lipids: the risk triad for atherosclerosis in gout. (1/543)
(+info)Involvement of the AIM2, NLRC4, and NLRP3 inflammasomes in caspase-1 activation by Listeria monocytogenes. (2/543)
(+info)Quantitative expression of RIG-like helicase, NOD-like receptor and inflammasome-related mRNAs in humans and mice. (3/543)
(+info)TLR5 activation induces secretory interleukin-1 receptor antagonist (sIL-1Ra) and reduces inflammasome-associated tissue damage. (4/543)
(+info)Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer disease. (5/543)
(+info)NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. (6/543)
(+info)Response of swine spleen to Streptococcus suis infection revealed by transcription analysis. (7/543)
(+info)Protein kinase A regulates caspase-1 via Ets-1 in bone stromal cell-derived lesions: a link between cyclic AMP and pro-inflammatory pathways in osteoblast progenitors. (8/543)
(+info)An inflammasome is a large cytosolic protein complex that plays a crucial role in the innate immune system's response to infection and stress. It is responsible for the activation of caspase-1, which subsequently leads to the processing and secretion of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18, and the induction of a form of cell death known as pyroptosis.
The inflammasome is formed when certain pattern recognition receptors (PRRs), such as NOD-like receptors (NLRs) or AIM2-like receptors (ALRs), recognize specific pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). This interaction results in the recruitment and assembly of the inflammasome complex, which includes the adaptor protein ASC and pro-caspase-1.
Once activated, caspase-1 cleaves pro-IL-1β and pro-IL-18 into their active forms, which are then released from the cell to recruit immune cells and initiate an inflammatory response. Dysregulation of inflammasome activation has been implicated in various diseases, including autoinflammatory disorders, autoimmune diseases, and neurodegenerative conditions.
Caspase-1 is a type of protease enzyme that plays a crucial role in the inflammatory response and programmed cell death, also known as apoptosis. It is produced as an inactive precursor protein, which is then cleaved into its active form by other proteases or through self-cleavage.
Once activated, caspase-1 helps to process and activate several pro-inflammatory cytokines, such as interleukin (IL)-1β and IL-18, which are involved in the recruitment of immune cells to sites of infection or tissue damage. Caspase-1 also contributes to programmed cell death by cleaving and activating other caspases, leading to the controlled destruction of the cell.
Dysregulation of caspase-1 has been implicated in various inflammatory diseases, such as autoimmune disorders and neurodegenerative conditions. Therefore, understanding the mechanisms that regulate caspase-1 activity is an important area of research for developing new therapeutic strategies to treat these diseases.
Interleukin-1 beta (IL-1β) is a member of the interleukin-1 cytokine family and is primarily produced by activated macrophages in response to inflammatory stimuli. It is a crucial mediator of the innate immune response and plays a key role in the regulation of various biological processes, including cell proliferation, differentiation, and apoptosis. IL-1β is involved in the pathogenesis of several inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis. It exerts its effects by binding to the interleukin-1 receptor, which triggers a signaling cascade that leads to the activation of various transcription factors and the expression of target genes.
Nod signaling adaptor proteins are a group of intracellular molecules that play a crucial role in the activation of immune responses to bacterial infections. These proteins are involved in the Nod-like receptor (NLR) signaling pathway, which is a key component of the innate immune system.
Nod signaling adaptor proteins include proteins such as Nod1, Nod2, and RIP2 (receptor-interacting protein 2). These proteins contain domains that allow them to interact with other molecules involved in the NLR signaling pathway, including Nod-like receptors, which are sensors of bacterial components such as peptidoglycan.
When Nod-like receptors detect the presence of bacterial components, they recruit and activate Nod signaling adaptor proteins, leading to the activation of downstream signaling pathways that ultimately result in the production of proinflammatory cytokines and the activation of immune cells. This helps to initiate an effective immune response against the invading bacteria.
Defects in Nod signaling adaptor proteins have been linked to various immune-related disorders, including susceptibility to bacterial infections and inflammatory diseases such as Crohn's disease.
Interleukin-18 (IL-18) is a pro-inflammatory cytokine, a type of signaling molecule used in intercellular communication. It belongs to the interleukin-1 (IL-1) family and is primarily produced by macrophages, although other cells such as keratinocytes, osteoblasts, and Kupffer cells can also produce it.
IL-18 plays a crucial role in the innate and adaptive immune responses. It contributes to the differentiation of Th1 (T helper 1) cells, which are critical for fighting intracellular pathogens, and enhances the cytotoxic activity of natural killer (NK) cells and CD8+ T cells. IL-18 also has a role in the production of interferon-gamma (IFN-γ), a cytokine that activates immune cells and has antiviral properties.
Dysregulation of IL-18 has been implicated in several inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. It is also involved in the pathogenesis of some autoimmune disorders and has been investigated as a potential therapeutic target for these conditions.
CARD (caspase recruitment domain) signaling adaptor proteins are a group of intracellular signaling molecules that play a crucial role in the regulation of various cellular processes, including inflammation, immunity, and programmed cell death or apoptosis. These proteins contain a CARD domain, which is a protein-protein interaction module that enables them to bind to other CARD-containing proteins and form large signaling complexes.
CARD signaling adaptor proteins function as molecular scaffolds that help bring together various signaling components in response to different stimuli, such as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). By doing so, they facilitate the activation of downstream signaling cascades and the initiation of appropriate cellular responses.
Some examples of CARD signaling adaptor proteins include:
1. Myeloid differentiation factor 88 (MyD88): This protein is involved in the signaling pathways of most Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) family members, which are critical for the detection of microbial components and the initiation of innate immune responses.
2. CARD9: This protein is involved in the signaling pathways of several C-type lectin receptors (CLRs), which recognize fungal and other pathogens, and plays a key role in antifungal immunity.
3. ASC (apoptosis-associated speck-like protein containing a CARD): This protein is involved in the formation of inflammasomes, which are large cytosolic complexes that activate caspase-1 and promote the maturation and secretion of proinflammatory cytokines.
4. RIPK2 (receptor-interacting serine/threonine-protein kinase 2): This protein is involved in the signaling pathways of NOD1 and NOD2, which are intracellular sensors of bacterial peptidoglycan, and plays a role in the regulation of inflammation and apoptosis.
Overall, CARD-containing proteins play crucial roles in various immune signaling pathways by mediating protein-protein interactions and downstream signal transduction events, ultimately leading to the activation of innate immunity and inflammatory responses.
Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of rare, hereditary autoinflammatory disorders caused by mutations in the NLRP3 gene, which encodes the cryopyrin protein. The mutation leads to overactivation of the inflammasome, an intracellular complex that regulates the activation of inflammatory cytokines, resulting in uncontrolled inflammation.
CAPS include three clinical subtypes:
1. Familial Cold Autoinflammatory Syndrome (FCAS): This is the mildest form of CAPS and typically presents in infancy or early childhood with recurrent episodes of fever, urticaria-like rash, and joint pain triggered by cold exposure.
2. Muckle-Wells Syndrome (MWS): This subtype is characterized by more severe symptoms than FCAS, including recurrent fever, urticaria-like rash, joint pain, and progressive hearing loss. Patients with MWS are also at risk for developing amyloidosis, a serious complication that can lead to kidney failure.
3. Neonatal-Onset Multisystem Inflammatory Disease (NOMID): Also known as chronic infantile neurological cutaneous and articular syndrome (CINCA), this is the most severe form of CAPS. It presents at birth or in early infancy with fever, urticaria-like rash, joint inflammation, and central nervous system involvement, including chronic meningitis, developmental delay, and hearing loss.
Treatment for CAPS typically involves targeted therapies that block the overactive inflammasome, such as IL-1 inhibitors. Early diagnosis and treatment can help prevent long-term complications and improve quality of life for patients with these disorders.
Hereditary autoinflammatory diseases (HAIDs) are a group of rare, inherited disorders characterized by recurrent episodes of inflammation in the body. These diseases are caused by mutations in genes that regulate the innate immune system, which is the body's first line of defense against infection.
In HAIDs, the immune system mistakenly attacks the body's own cells and tissues, leading to symptoms such as fever, rash, joint pain and swelling, abdominal pain, and inflammation of internal organs. The symptoms can vary in severity and frequency, and may be triggered by factors such as stress, infection, or physical exertion.
Examples of HAIDs include Familial Mediterranean Fever (FMF), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Cryopyrin-Associated Periodic Syndromes (CAPS), and Blau syndrome/Early Onset Sarcoidosis.
The diagnosis of HAIDs is often challenging due to the rarity of these conditions and overlapping symptoms with other diseases. Genetic testing, medical history, physical examination, and laboratory tests are used to confirm the diagnosis and determine the specific type of HAID. Treatment typically involves medications that suppress the overactive immune system, such as biologic agents that target specific components of the immune system.
Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).
Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.
Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.
Pattern recognition receptors (PRRs) are a type of receptor found on the surface of various immune cells, including dendritic cells, macrophages, and neutrophils. These receptors recognize specific patterns or motifs that are typically associated with pathogens such as bacteria, viruses, fungi, and parasites.
PRRs can be divided into several different classes based on their structure and function, including toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), retinoic acid-inducible gene I-like receptors (RLRs), and C-type lectin receptors (CLRs).
When a PRR recognizes a pathogen-associated molecular pattern (PAMP), it triggers a series of intracellular signaling events that ultimately lead to the activation of immune responses, such as the production of proinflammatory cytokines and the activation of adaptive immunity.
Overall, PRRs play a critical role in the early detection and response to pathogens, helping to prevent or limit infection and disease.
Apoptosis regulatory proteins are a group of proteins that play an essential role in the regulation and execution of apoptosis, also known as programmed cell death. This process is a normal part of development and tissue homeostasis, allowing for the elimination of damaged or unnecessary cells. The balance between pro-apoptotic and anti-apoptotic proteins determines whether a cell will undergo apoptosis.
Pro-apoptotic proteins, such as BAX, BID, and PUMA, promote apoptosis by neutralizing or counteracting the effects of anti-apoptotic proteins or by directly activating the apoptotic pathway. These proteins can be activated in response to various stimuli, including DNA damage, oxidative stress, and activation of the death receptor pathway.
Anti-apoptotic proteins, such as BCL-2, BCL-XL, and MCL-1, inhibit apoptosis by binding and neutralizing pro-apoptotic proteins or by preventing the release of cytochrome c from the mitochondria, which is a key step in the intrinsic apoptotic pathway.
Dysregulation of apoptosis regulatory proteins has been implicated in various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases. Therefore, understanding the role of these proteins in apoptosis regulation is crucial for developing new therapeutic strategies to treat these conditions.
NAIP (Neuronal Apoptosis Inhibitory Protein) is a protein involved in inhibiting programmed cell death, also known as apoptosis. It is a member of the inhibitor of apoptosis (IAP) family and is primarily expressed in neurons. NAIP plays a crucial role in preventing excessive cell death during nervous system development and after nerve injury. It functions by binding to and inhibiting certain caspases, which are enzymes that play an essential role in initiating and executing apoptosis. Mutations in the gene encoding NAIP have been associated with neurodegenerative disorders such as spinal muscular atrophy and amyotrophic lateral sclerosis (ALS).
Inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is characterized by the following signs: rubor (redness), tumor (swelling), calor (heat), dolor (pain), and functio laesa (loss of function). The process involves the activation of the immune system, recruitment of white blood cells, and release of inflammatory mediators, which contribute to the elimination of the injurious stimuli and initiation of the healing process. However, uncontrolled or chronic inflammation can also lead to tissue damage and diseases.
Calcium-binding proteins (CaBPs) are a diverse group of proteins that have the ability to bind calcium ions (Ca^2+^) with high affinity and specificity. They play crucial roles in various cellular processes, including signal transduction, muscle contraction, neurotransmitter release, and protection against oxidative stress.
The binding of calcium ions to these proteins induces conformational changes that can either activate or inhibit their functions. Some well-known CaBPs include calmodulin, troponin C, S100 proteins, and parvalbumins. These proteins are essential for maintaining calcium homeostasis within cells and for mediating the effects of calcium as a second messenger in various cellular signaling pathways.
Innate immunity, also known as non-specific immunity or natural immunity, is the inherent defense mechanism that provides immediate protection against potentially harmful pathogens (like bacteria, viruses, fungi, and parasites) without the need for prior exposure. This type of immunity is present from birth and does not adapt to specific threats over time.
Innate immune responses involve various mechanisms such as:
1. Physical barriers: Skin and mucous membranes prevent pathogens from entering the body.
2. Chemical barriers: Enzymes, stomach acid, and lysozyme in tears, saliva, and sweat help to destroy or inhibit the growth of microorganisms.
3. Cellular responses: Phagocytic cells (neutrophils, monocytes, macrophages) recognize and engulf foreign particles and pathogens, while natural killer (NK) cells target and eliminate virus-infected or cancerous cells.
4. Inflammatory response: When an infection occurs, the innate immune system triggers inflammation to increase blood flow, recruit immune cells, and remove damaged tissue.
5. Complement system: A group of proteins that work together to recognize and destroy pathogens directly or enhance phagocytosis by coating them with complement components (opsonization).
Innate immunity plays a crucial role in initiating the adaptive immune response, which is specific to particular pathogens and provides long-term protection through memory cells. Both innate and adaptive immunity work together to maintain overall immune homeostasis and protect the body from infections and diseases.
Cytoskeletal proteins are a type of structural proteins that form the cytoskeleton, which is the internal framework of cells. The cytoskeleton provides shape, support, and structure to the cell, and plays important roles in cell division, intracellular transport, and maintenance of cell shape and integrity.
There are three main types of cytoskeletal proteins: actin filaments, intermediate filaments, and microtubules. Actin filaments are thin, rod-like structures that are involved in muscle contraction, cell motility, and cell division. Intermediate filaments are thicker than actin filaments and provide structural support to the cell. Microtubules are hollow tubes that are involved in intracellular transport, cell division, and maintenance of cell shape.
Cytoskeletal proteins are composed of different subunits that polymerize to form filamentous structures. These proteins can be dynamically assembled and disassembled, allowing cells to change their shape and move. Mutations in cytoskeletal proteins have been linked to various human diseases, including cancer, neurological disorders, and muscular dystrophies.
Macrophages are a type of white blood cell that are an essential part of the immune system. They are large, specialized cells that engulf and destroy foreign substances, such as bacteria, viruses, parasites, and fungi, as well as damaged or dead cells. Macrophages are found throughout the body, including in the bloodstream, lymph nodes, spleen, liver, lungs, and connective tissues. They play a critical role in inflammation, immune response, and tissue repair and remodeling.
Macrophages originate from monocytes, which are a type of white blood cell produced in the bone marrow. When monocytes enter the tissues, they differentiate into macrophages, which have a larger size and more specialized functions than monocytes. Macrophages can change their shape and move through tissues to reach sites of infection or injury. They also produce cytokines, chemokines, and other signaling molecules that help coordinate the immune response and recruit other immune cells to the site of infection or injury.
Macrophages have a variety of surface receptors that allow them to recognize and respond to different types of foreign substances and signals from other cells. They can engulf and digest foreign particles, bacteria, and viruses through a process called phagocytosis. Macrophages also play a role in presenting antigens to T cells, which are another type of immune cell that helps coordinate the immune response.
Overall, macrophages are crucial for maintaining tissue homeostasis, defending against infection, and promoting wound healing and tissue repair. Dysregulation of macrophage function has been implicated in a variety of diseases, including cancer, autoimmune disorders, and chronic inflammatory conditions.
Bacterial secretion systems are specialized molecular machines that allow bacteria to transport proteins and other molecules across their cell membranes. These systems play a crucial role in bacterial survival, pathogenesis, and communication with their environment. They are composed of several protein components organized into complex structures that span the bacterial cell envelope.
There are several types of bacterial secretion systems, including type I to type IX secretion systems (T1SS to T9SS). Each type has a unique structure and mechanism for transporting specific substrates across the membrane. Here are some examples:
* Type II secretion system (T2SS): This system transports folded proteins across the outer membrane of gram-negative bacteria. It is composed of 12 to 15 protein components that form a complex structure called the secretion apparatus or "secretion nanomachine." The T2SS secretes various virulence factors, such as exotoxins and hydrolases, which contribute to bacterial pathogenesis.
* Type III secretion system (T3SS): This system transports effector proteins directly into the cytosol of host cells during bacterial infection. It is composed of a hollow needle-like structure that extends from the bacterial cell surface and injects effectors into the host cell. The T3SS plays a critical role in the pathogenesis of many gram-negative bacteria, including Yersinia, Salmonella, and Shigella.
* Type IV secretion system (T4SS): This system transports DNA or proteins across the bacterial cell envelope and into target cells. It is composed of a complex structure that spans both the inner and outer membranes of gram-negative bacteria and the cytoplasmic membrane of gram-positive bacteria. The T4SS plays a role in bacterial conjugation, DNA uptake and release, and delivery of effector proteins to host cells.
* Type VI secretion system (T6SS): This system transports effector proteins into neighboring cells or the extracellular environment. It is composed of a contractile sheath-tube structure that propels effectors through a hollow inner tube and out of the bacterial cell. The T6SS plays a role in interbacterial competition, biofilm formation, and virulence.
Overall, these secretion systems play crucial roles in bacterial survival, pathogenesis, and communication with their environment. Understanding how they function and how they contribute to bacterial infection and disease is essential for developing new strategies to combat bacterial infections and improve human health.
Flagellin is a protein that makes up the structural filament of the flagellum, which is a whip-like structure found on many bacteria that enables them to move. It is also known as a potent stimulator of the innate immune response and can be recognized by Toll-like receptor 5 (TLR5) in the host's immune system, triggering an inflammatory response. Flagellin is highly conserved among different bacterial species, making it a potential target for broad-spectrum vaccines and immunotherapies against bacterial infections.
Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.
The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.
Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.
"Legionella pneumophila" is a species of Gram-negative, aerobic bacteria that are commonly found in freshwater environments such as lakes and streams. It can also be found in man-made water systems like hot tubs, cooling towers, and decorative fountains. This bacterium is the primary cause of Legionnaires' disease, a severe form of pneumonia, and Pontiac fever, a milder illness resembling the flu. Infection typically occurs when people inhale tiny droplets of water containing the bacteria. It is not transmitted from person to person.
Medical Definition of "Multiprotein Complexes" :
Multiprotein complexes are large molecular assemblies composed of two or more proteins that interact with each other to carry out specific cellular functions. These complexes can range from relatively simple dimers or trimers to massive structures containing hundreds of individual protein subunits. They are formed through a process known as protein-protein interaction, which is mediated by specialized regions on the protein surface called domains or motifs.
Multiprotein complexes play critical roles in many cellular processes, including signal transduction, gene regulation, DNA replication and repair, protein folding and degradation, and intracellular transport. The formation of these complexes is often dynamic and regulated in response to various stimuli, allowing for precise control of their function.
Disruption of multiprotein complexes can lead to a variety of diseases, including cancer, neurodegenerative disorders, and infectious diseases. Therefore, understanding the structure, composition, and regulation of these complexes is an important area of research in molecular biology and medicine.
Adaptor proteins are a type of protein that play a crucial role in intracellular signaling pathways by serving as a link between different components of the signaling complex. Specifically, "signal transducing adaptor proteins" refer to those adaptor proteins that are involved in signal transduction processes, where they help to transmit signals from the cell surface receptors to various intracellular effectors. These proteins typically contain modular domains that allow them to interact with multiple partners, thereby facilitating the formation of large signaling complexes and enabling the integration of signals from different pathways.
Signal transducing adaptor proteins can be classified into several families based on their structural features, including the Src homology 2 (SH2) domain, the Src homology 3 (SH3) domain, and the phosphotyrosine-binding (PTB) domain. These domains enable the adaptor proteins to recognize and bind to specific motifs on other signaling molecules, such as receptor tyrosine kinases, G protein-coupled receptors, and cytokine receptors.
One well-known example of a signal transducing adaptor protein is the growth factor receptor-bound protein 2 (Grb2), which contains an SH2 domain that binds to phosphotyrosine residues on activated receptor tyrosine kinases. Grb2 also contains an SH3 domain that interacts with proline-rich motifs on other signaling proteins, such as the guanine nucleotide exchange factor SOS. This interaction facilitates the activation of the Ras small GTPase and downstream signaling pathways involved in cell growth, differentiation, and survival.
Overall, signal transducing adaptor proteins play a critical role in regulating various cellular processes by modulating intracellular signaling pathways in response to extracellular stimuli. Dysregulation of these proteins has been implicated in various diseases, including cancer and inflammatory disorders.
A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.
Nuclear proteins are a category of proteins that are primarily found in the nucleus of a eukaryotic cell. They play crucial roles in various nuclear functions, such as DNA replication, transcription, repair, and RNA processing. This group includes structural proteins like lamins, which form the nuclear lamina, and regulatory proteins, such as histones and transcription factors, that are involved in gene expression. Nuclear localization signals (NLS) often help target these proteins to the nucleus by interacting with importin proteins during active transport across the nuclear membrane.
C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.
The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.
C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.
One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.
Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.
Cell death is the process by which cells cease to function and eventually die. There are several ways that cells can die, but the two most well-known and well-studied forms of cell death are apoptosis and necrosis.
Apoptosis is a programmed form of cell death that occurs as a normal and necessary process in the development and maintenance of healthy tissues. During apoptosis, the cell's DNA is broken down into small fragments, the cell shrinks, and the membrane around the cell becomes fragmented, allowing the cell to be easily removed by phagocytic cells without causing an inflammatory response.
Necrosis, on the other hand, is a form of cell death that occurs as a result of acute tissue injury or overwhelming stress. During necrosis, the cell's membrane becomes damaged and the contents of the cell are released into the surrounding tissue, causing an inflammatory response.
There are also other forms of cell death, such as autophagy, which is a process by which cells break down their own organelles and proteins to recycle nutrients and maintain energy homeostasis, and pyroptosis, which is a form of programmed cell death that occurs in response to infection and involves the activation of inflammatory caspases.
Cell death is an important process in many physiological and pathological processes, including development, tissue homeostasis, and disease. Dysregulation of cell death can contribute to the development of various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases.
Immunological models are simplified representations or simulations of the immune system's structure, function, and interactions with pathogens or other entities. These models can be theoretical (conceptual), mathematical, or computational and are used to understand, explain, and predict immunological phenomena. They help researchers study complex immune processes and responses that cannot be easily observed or manipulated in vivo.
Theoretical immunological models provide conceptual frameworks for understanding immune system behavior, often using diagrams or flowcharts to illustrate interactions between immune components. Mathematical models use mathematical equations to describe immune system dynamics, allowing researchers to simulate and analyze the outcomes of various scenarios. Computational models, also known as in silico models, are created using computer software and can incorporate both theoretical and mathematical concepts to create detailed simulations of immunological processes.
Immunological models are essential tools for advancing our understanding of the immune system and developing new therapies and vaccines. They enable researchers to test hypotheses, explore the implications of different assumptions, and identify areas requiring further investigation.
Inflammation mediators are substances that are released by the body in response to injury or infection, which contribute to the inflammatory response. These mediators include various chemical factors such as cytokines, chemokines, prostaglandins, leukotrienes, and histamine, among others. They play a crucial role in regulating the inflammatory process by attracting immune cells to the site of injury or infection, increasing blood flow to the area, and promoting the repair and healing of damaged tissues. However, an overactive or chronic inflammatory response can also contribute to the development of various diseases and conditions, such as autoimmune disorders, cardiovascular disease, and cancer.
Cathepsin B is a lysosomal cysteine protease that plays a role in various physiological processes, including intracellular protein degradation, antigen presentation, and extracellular matrix remodeling. It is produced as an inactive precursor (procathepsin B) and activated upon cleavage of the propeptide by other proteases or autocatalytically. Cathepsin B has a wide range of substrates, including collagen, elastin, and various intracellular proteins. Its dysregulation has been implicated in several pathological conditions, such as cancer, neurodegenerative diseases, and inflammatory disorders.
Autoimmunity is a medical condition in which the body's immune system mistakenly attacks and destroys healthy tissues within the body. In normal function, the immune system recognizes and fights off foreign substances such as bacteria, viruses, and toxins. However, when autoimmunity occurs, the immune system identifies self-molecules or tissues as foreign and produces an immune response against them.
This misguided response can lead to chronic inflammation, tissue damage, and impaired organ function. Autoimmune diseases can affect various parts of the body, including the joints, skin, glands, muscles, and blood vessels. Some common examples of autoimmune diseases are rheumatoid arthritis, lupus, multiple sclerosis, type 1 diabetes, Hashimoto's thyroiditis, and Graves' disease.
The exact cause of autoimmunity is not fully understood, but it is believed to involve a combination of genetic, environmental, and lifestyle factors that trigger an abnormal immune response in susceptible individuals. Treatment for autoimmune diseases typically involves managing symptoms, reducing inflammation, and suppressing the immune system's overactive response using medications such as corticosteroids, immunosuppressants, and biologics.
Host-pathogen interactions refer to the complex and dynamic relationship between a living organism (the host) and a disease-causing agent (the pathogen). This interaction can involve various molecular, cellular, and physiological processes that occur between the two entities. The outcome of this interaction can determine whether the host will develop an infection or not, as well as the severity and duration of the illness.
During host-pathogen interactions, the pathogen may release virulence factors that allow it to evade the host's immune system, colonize tissues, and obtain nutrients for its survival and replication. The host, in turn, may mount an immune response to recognize and eliminate the pathogen, which can involve various mechanisms such as inflammation, phagocytosis, and the production of antimicrobial agents.
Understanding the intricacies of host-pathogen interactions is crucial for developing effective strategies to prevent and treat infectious diseases. This knowledge can help identify new targets for therapeutic interventions, inform vaccine design, and guide public health policies to control the spread of infectious agents.
Autophagy is a fundamental cellular process that involves the degradation and recycling of damaged or unnecessary cellular components, such as proteins and organelles. The term "autophagy" comes from the Greek words "auto" meaning self and "phagy" meaning eating. It is a natural process that occurs in all types of cells and helps maintain cellular homeostasis by breaking down and recycling these components.
There are several different types of autophagy, including macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Macroautophagy is the most well-known form and involves the formation of a double-membraned vesicle called an autophagosome, which engulfs the cellular component to be degraded. The autophagosome then fuses with a lysosome, an organelle containing enzymes that break down and recycle the contents of the autophagosome.
Autophagy plays important roles in various cellular processes, including adaptation to starvation, removal of damaged organelles, clearance of protein aggregates, and regulation of programmed cell death (apoptosis). Dysregulation of autophagy has been implicated in a number of diseases, including cancer, neurodegenerative disorders, and infectious diseases.
Caspases are a family of protease enzymes that play essential roles in programmed cell death, also known as apoptosis. These enzymes are produced as inactive precursors and are activated when cells receive signals to undergo apoptosis. Once activated, caspases cleave specific protein substrates, leading to the characteristic morphological changes and DNA fragmentation associated with apoptotic cell death. Caspases also play roles in other cellular processes, including inflammation and differentiation. There are two types of caspases: initiator caspases (caspase-2, -8, -9, and -10) and effector caspases (caspase-3, -6, and -7). Initiator caspases are activated in response to various apoptotic signals and then activate the effector caspases, which carry out the proteolytic cleavage of cellular proteins. Dysregulation of caspase activity has been implicated in a variety of diseases, including neurodegenerative disorders, ischemic injury, and cancer.
Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.
For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.
Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.
Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.
Cytokines are a broad and diverse category of small signaling proteins that are secreted by various cells, including immune cells, in response to different stimuli. They play crucial roles in regulating the immune response, inflammation, hematopoiesis, and cellular communication.
Cytokines mediate their effects by binding to specific receptors on the surface of target cells, which triggers intracellular signaling pathways that ultimately result in changes in gene expression, cell behavior, and function. Some key functions of cytokines include:
1. Regulating the activation, differentiation, and proliferation of immune cells such as T cells, B cells, natural killer (NK) cells, and macrophages.
2. Coordinating the inflammatory response by recruiting immune cells to sites of infection or tissue damage and modulating their effector functions.
3. Regulating hematopoiesis, the process of blood cell formation in the bone marrow, by controlling the proliferation, differentiation, and survival of hematopoietic stem and progenitor cells.
4. Modulating the development and function of the nervous system, including neuroinflammation, neuroprotection, and neuroregeneration.
Cytokines can be classified into several categories based on their structure, function, or cellular origin. Some common types of cytokines include interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), chemokines, colony-stimulating factors (CSFs), and transforming growth factors (TGFs). Dysregulation of cytokine production and signaling has been implicated in various pathological conditions, such as autoimmune diseases, chronic inflammation, cancer, and neurodegenerative disorders.
Inflammasome
Pattern recognition receptor
NOD-like receptor
Immune system
NLRP
Pyroptosis
Dapansutrile
AIM2
Jürg Tschopp
Jonathan C. Kagan
Inflammaging
Interleukin-1 family
Guanylate-binding protein
Caspase 4
Caspase
Caspase 11
NLRP3
Caspase 5
Vitiligo
Shake it Up Australia Foundation
Gladstone Institutes
NLRP7
Bat virome
Vishva Dixit
Periodic fever syndrome
NFE2L2
Clare Bryant
NLRC4
M2 proton channel
Signalosome
Inflammasome - Wikipedia
The inflammasomes: guardians of the body
The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation
Resveratrol Inhibits Ischemia-Induced Myocardial Senescence Signals and NLRP3 Inflammasome Activation
The inflammasome and its role in infections | Frontiers Research Topic
Halia Therapeutics to Present at the 5th Inflammasome Therapeutics Summit
Halia Therapeutics to Present at the 5th Inflammasome Therapeutics Summit
Halia Therapeutics to Present at the 5th Inflammasome Therapeutics Summit
The Molecular Basis for Inflammasome Activation - CEMIR - NTNU
ASC-GFP Reporter Monocytes | Inflammasomes | InvivoGen
A PRACTICAL GUIDE TO UNDERSTANDING INFLAMMASOMES | InvivoGen
Pharma Looks to Inflammasome Inhibitors as All-Around Therapies | The Scientist Magazine®
talks.cam : Cross-species investigation of the inflammasome
Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes...
Halia Therapeutics to Present at the 5th Inflammasome Therapeutics Summit
Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome
Intracellular Invasion of Orientia tsutsugamushi Activates Inflammasome in ASC-Dependent Manner
Blocking Inflammasome-induced Neuroinflammation in Parkinson's Disease with a Potent, Orally Available Small Molecule |...
NLR family pyrin domain containing 3 (NLRP3) inflammasomes and peripheral neuropathic pain - Emphasis on microRNAs (miRNAs) as...
Halia Therapeutics to Present at the 5th Inflammasome Therapeutics Summit
Sparstolonin B Exerts Therapeutic Effects on Collagen-Induced Arthritis by Inhibiting the NLRP3 Inflammasome and Reducing the...
Zinc inhibits high glucose-induced NLRP3 inflammasome activation in human peritoneal mesothelial cells
NLRP3 inflammasome blockade... - Researchers - ANU
Bamboo Vinegar Decreases Inflammatory Mediator Expression and NLRP3 Inflammasome Activation by Inhibiting Reactive Oxygen...
Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma...
A human-specific motif facilitates CARD8 inflammasome activation after HIV-1 infection | Fred Hutchinson Cancer Center
Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation ...
DISSECTING MECHANISMS OF NLRP3 INFLAMMASOME REGULATION - Research Explorer The University of Manchester
Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive...
Inflammasome Signaling | Journal of Experimental Medicine | Rockefeller University Press
NLRP3 Inflammasome Activation10
- In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3. (nih.gov)
- Zinc (Zn) deficiency is important for inducing nucleotide-binding domain and leucine‑rich repeat‑containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation in macrophages. (spandidos-publications.com)
- However, its function in the NLRP3 inflammasome activation of peritoneal mesothelial cells (PMCs) remains to be elucidated. (spandidos-publications.com)
- It was found that Zn supplementation inhibited HG‑induced NLRP3 inflammasome activation in the HPMCs by attenuating ROS production. (spandidos-publications.com)
- These results indicated that Zn inhibited NLRP3 inflammasome activation in the HG‑treated HPMCs by activating the Nrf2 antioxidant pathway and reducing the production of ROS. (spandidos-publications.com)
- Fan Y, Zhang X, Yang L, Wang J, Hu Y, Bian A, Liu J and Ma J: Zinc inhibits high glucose-induced NLRP3 inflammasome activation in human peritoneal mesothelial cells. (spandidos-publications.com)
- We show that metformin inhibited NLRP3 inflammasome activation and interleukin (IL)-1β production in cultured and alveolar macrophages along with inflammasome-independent IL-6 secretion, thus attenuating lipopolysaccharide (LPS)- and SARS-CoV-2-induced ARDS. (lu.se)
- This thesis aimed to further our understanding on the mode and regulation of NLRP3 inflammasome activation. (manchester.ac.uk)
- Here, we propose that NLRP3 inflammasome-dependent pyroptosis may be involved in the mechanism of age-dependent isoflurane-induced cognitive impairment and discuss that inhibiting NLRP3 inflammasome activation with a novel inhibitor MCC950 may ameliorate age-dependent isoflurane-induced neuro-inflammation. (biomedcentral.com)
- Role of engineered metal oxide nanoparticle agglomeration in reactive oxygen species generation and cathepsin B release in NLRP3 inflammasome activation and pulmonary toxicity. (cdc.gov)
Macrophages6
- Traditionally, inflammasomes have mainly been studied in professional immune cells of the innate immune system, such as macrophages. (wikipedia.org)
- Here we show that beta cell failure in adult ZDF rats is not associated with CB 1 R signaling in beta cells, but rather in M1 macrophages infiltrating into pancreatic islets, and that this leads to activation of the Nlrp3-ASC inflammasome in the macrophages. (nature.com)
- We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS. (diva-portal.org)
- O. tsutsugamushi infection induces production of pro-inflammatory mediators including interleukin-1β (IL-1β), which is secreted mainly from macrophages upon cytosolic stimuli by activating cysteine protease caspase-1 within a complex called the inflammasome, and is a key player in initiating and maintaining the inflammatory response. (harvard.edu)
- Here, we show that asthma exacerbation is triggered by airway macrophages through a prion-like cell-to-cell transmission of extracellular particulates, including ASC protein, that assemble inflammasomes and mediate IL-1β production. (jci.org)
- NLRC4 inflammasome present in macrophages, neutrophils, and intestinal epithelial cells mediates substrate cleavage via CASP1 or CASP8 to induce effector programs, including the release of inflammatory mediators and pyroptosis. (creative-bioarray.com)
Caspase28
- Through their caspase activation and recruitment domain (CARD) or pyrin domain (PYD), the inflammasome receptors interact with the adaptor protein ASC, which then recruits pro-caspase-1 via its CARD domain and activates the effector caspase through proteolytic cleavage. (wikipedia.org)
- In addition to these so-called canonical inflammasomes, different studies also described non-canonical inflammasome complexes that act independently of caspase-1. (wikipedia.org)
- In mice, the non-canonical inflammasome is activated by direct sensing of cytosolic bacterial lipopolysaccharide (LPS) by caspase-11, which subsequently induces pyroptotic cell death. (wikipedia.org)
- In human cells, the corresponding caspases of the non-canonical inflammasome are caspase 4 and caspase 5. (wikipedia.org)
- Once active, the inflammasome binds to pro-caspase-1 (the precursor molecule of caspase-1), either homotypically via its own caspase activation and recruitment domain (CARD) or via the CARD of the adaptor protein ASC which it binds to during inflammasome formation. (wikipedia.org)
- In its full form, the inflammasome appositions together many p45 pro-caspase-1 molecules, inducing their autocatalytic cleavage into p20 and p10 subunits. (wikipedia.org)
- The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. (nih.gov)
- Mechanistically, the inflammasome promotes the activation of caspase 1 and the secretion and accumulation of proinflammatory cytokines such as interleukin- (IL-) 1 β and IL-18 [ 3 ]. (hindawi.com)
- Most NLRs assemble in large multiprotein complex called the inflammasome leading to the activation of caspase-1. (frontiersin.org)
- Inflammasomes are multi-molecular complexes that process pro-caspase-1 into the active enzyme. (ntnu.edu)
- Completed and published a study on the roles of caspase-8 and RIP kinases inflammasome activation, NF-κB activation and cell death in response to bacterial infection. (ntnu.edu)
- ASC's bipartite composition, consisting of one PYD and one CARD domain, allows the recruitment of the CARD-containing pro-caspase-1 to canonical inflammasome sensors that do not contain a CARD domain, such as NLRP3, AIM2, and Pyrin [1]. (invivogen.com)
- THP-1 cells are widely used for inflammasome studies due to their high expression levels of NLRP3, ASC, and pro-caspase-1. (invivogen.com)
- The activity of the NLRP3/caspase‑1 inflammasome was assessed via western blot analysis, immunofluorescence, reverse transcription‑quantitative polymerase chain reaction and ELISA. (spandidos-publications.com)
- Recently, it was reported that the caspase recruitment domain family member 8 (CARD8), an inflammasome sensor, plays a role in detecting HIV-1 infection. (fredhutch.org)
- Inflammasomes are intracellular mediators of inflammation through the activation of the cysteine protease caspase-1 and secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β). (manchester.ac.uk)
- Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. (ijbs.com)
- NLRP3 inflammasome is the most thoroughly studied one, which is composed of NLRP3, apoptosis associated speck like protein (ASC) and caspase-1 precursor (pro-caspase-1) (Figure 1 ) [ 5 - 10 ]. (ijbs.com)
- By activating caspase-1, NLRP3 inflammasome can induce the maturation and secretion of pro-inflammatory factors: Interleukin-1beta (IL-1β) and Interleukin-18 (IL-18). (ijbs.com)
- The second stimuli, including reactive oxygen species (ROS) production, intracellular potassium (K + ) concentration and the distuption of lysosomal membrane, promotes the assembly of inflammasome and leads to the activation of caspase-1, which can catalyze the pro-IL-1β into active IL-1β [ 1 , 9 , 13 - 15 ]. (ijbs.com)
- Sensing and reacting to dangers by caspases: Caspase activation via inflammasomes. (ddtjournal.com)
- Creative Bioarray can provide customers with inducing NLRC4 inflammasome activation services and detection services of ASC, NLRC4, caspase-1, GSDMD, IL-1β, IL-18 and other proteins or genes. (creative-bioarray.com)
- Creative Bioarray uses methods such as PCR, Western Blot, and ELISA to help you detect the expression levels of pyroptosis-related genes or proteins during NLRC4 inflammasome activation, such as NLRC4, caspase-1, ASC, GSDMD, IL-1β , IL-18 etc. (creative-bioarray.com)
- In the sensing step, PAMPs and DAMPs are first recognized by the inflammasome and form the inflammasome complex with pro-caspase-1 [ 2 ]. (thno.org)
- Then, in the activation step, the inflammasome complex (IC) activates caspase-1 that cleaves Gasdermin D (GSDMD) and proinflammatory cytokines IL-1β and IL-18. (thno.org)
- We have previously shown that isoflurane induces activation of NLRP3, cleavage of caspase 1, and increase of IL-1β and TNF-α levels in the hippocampus of aging mice and supposed that inhibiting the NLRP3 inflammasome might have therapeutic merit for ameliorating general anesthesia-induced cognitive deficits [ 5 ] as cited in Wang's study. (biomedcentral.com)
- However, Ac-YVAD-cmk is a specific inhibitor of caspase-1, not of NLRP3 inflammasome. (biomedcentral.com)
- The Nucleotide -binding oligomerization domain, Leucine -rich Repeat and Pyrin domain containing (NLRP) family and accompanying Inflammasomes are important intracellular receptors of inflammatory pathogens and stress signals that elevate caspase-1-mediated release of IL-1 ß and IL-18 . (bvsalud.org)
Secretion3
- Characterized new complexity in how bacteria containing type III secretion systems can manipulate multiple inflammasome pathways leading to IL-1β and IL-18 release. (ntnu.edu)
- These cells do not express the ASC protein and display a complete abrogation of mature IL-1β secretion upon activation of the canonical and non-canonical inflammasomes. (invivogen.com)
- Mehta, J.L. NLRP3 inflammasome via IL-1β regulates PCSK9 secretion: Erratum. (thno.org)
Inhibition4
- Halia's therapeutic inhibition of NLRP3 prevents the formation of the NLRP3 inflammasome and promotes its disassembly once formed, thereby inhibiting the production and release of IL-1β and IL-18. (wkrg.com)
- This study provides proof-of-concept that pharmacological inhibition of the NLRP3 inflammasome is a viable anti-hypertensive strategy. (monash.edu)
- We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity. (scienceopen.com)
- Inflammasome inhibition reverted the therapeutic failure of ICB in inflammasome-activated tumors. (thno.org)
Inhibiting the NLRP3 inflammasome1
- Sparstolonin B improved inflammatory responses and oxidative stress by inhibiting the NLRP3 inflammasome, inhibiting the expression of FucT-V and downregulating the TLR4/MYD88/NF-𝜅B signaling pathway in order to rescue RA. (hindawi.com)
Increased NLRP3 inflammasome expression1
- found that exposure of primed microglial cells or mice to manganese increased NLRP3 inflammasome expression and activation. (omniprex.com)
Pyroptosis5
- Here we provide a detailed review of the mechanisms whereby NLRP3 inflammasomes contribute to neuropathic pain via (1) neuroinflammation, (2) apoptosis, (3) pyroptosis, (4) proinflammatory cytokine release, (5) mitochondrial dysfunction, and (6) oxidative stress. (iasp-pain.org)
- We aim to help customers better study NLRC4 inflammasome-dependent pyroptosis. (creative-bioarray.com)
- Our services mainly include in vitro induction of NLRC4 inflammasome activation and NLRC4-dependent pyroptosis. (creative-bioarray.com)
- Inflammasomes refer to the cytoplasmic multimeric protein complexes that sense pathogen- or danger-associated molecular patterns (PAMPs or DAMPs, respectively) to mediate the inflammatory response and induce programmed cell death known as pyroptosis [ 1 ]. (thno.org)
- In this regard, we present a hypothesis that pyroptosis plays a critical role in the mechanism of isoflurane-induced cognitive impairment and MCC950 inhibits the NLRP3 inflammasome-dependent pyroptosis in isoflurane anesthesia to improve the cognition. (biomedcentral.com)
Mechanisms7
- Ultimately, the work on inflammasomes led to the current research field, where disease mechanisms and treatments are being investigated. (wikipedia.org)
- This conference is the largest gathering of inflammasome biopharma experts and pioneers and is intended to further understand mechanisms of the inflammasome pathway including NLRP1, NLRP3, and beyond, as well as furthering the discussion around new approaches to advance inflammasome therapeutics. (wkrg.com)
- The work in Theme two is focused on describing mechanisms leading to inflammasome activation, and to study implications on infectious and non-infectious inflammation. (ntnu.edu)
- 2017 . Molecular mechanisms of inflammasome signaling. (invivogen.com)
- To explore the role of α 1,3-fucosyltransferase in the mediation of rheumatoid arthritic inflammation, the protective effect of Sparstolonin B on rheumatoid arthritis (RA), and the mechanisms that regulate the NLRP3 inflammasome. (hindawi.com)
- This article reviewed the progress about the effects of H 2 S on NLRP3 inflammasome and its mechanisms involved in recent years to provide theoretical basis for in-depth study. (ijbs.com)
- These diseases were reclassified based on the innate immunity mechanisms and the inflammasome, a protein complex containing caspases involved in the proteolytic cleavage of interleukin (IL)-1 precursors to produce active forms of IL-1 (explaining the pathogenesis of fevers in these individuals) (see Table 1). (medscape.com)
Intracellular4
- On the other hand, the inflammasome response maybe absent in certain conditions, hence allowing some intracellular infections to pass unnoticed. (frontiersin.org)
- Many major biopharmaceutical companies are developing or acquiring drugs that target the NLRP3 inflammasome, a large intracellular complex that researchers say can spark inflammation and stoke diseases of lifestyle and aging. (the-scientist.com)
- Around the same time, a group of scientists at the University of Lausanne in Switzerland found that NALP1/NLRP1, a protein from the same family, forms a large intracellular complex called an inflammasome , which helps generate the IL-1β cytokine, triggering a cascade of inflammation. (the-scientist.com)
- A decade ago, inflammasome was described as a large intracellular signaling platform, which contains a cytoplasmic pattern recognition receptor, especially a nucleotide-binding oligomerization domain-like receptor (NLR). (ijbs.com)
NLRC46
- During that time, several other inflammasomes were discovered, two of which are also NLR subsets-NLRP3 and NLRC4. (wikipedia.org)
- NLRC4 inflammasome is involved in the body's innate immune response and plays an important role in immune regulation during infection with a variety of pathogens. (creative-bioarray.com)
- Flagellin, a component of bacterial flagella, plays an important role in the activation of the NLRC4 inflammasome, which can also be activated by aflagellate bacteria such as Shigella flexneri. (creative-bioarray.com)
- Structural, functional, and translational insights gleaned from the study of NLRC4 inflammasome. (creative-bioarray.com)
- Classic in vitro models of NLRC4 inflammasome activation include THP-1 and BMDM. (creative-bioarray.com)
- We complete the priming process by treating cells with LPS for several hours, followed by the addition of S. typhimurium or flagellin to stimulate NLRC4 inflammasome activation. (creative-bioarray.com)
Regulation3
- Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. (diva-portal.org)
- We then present the current research literature reporting on the antinociceptive effects of several natural products and pharmacological interventions that target activation, expression, and/or regulation of NLRP3 inflammasome. (iasp-pain.org)
- Inflammasome up-regulation and activation in dysferlin-deficient skeletal muscle. (bvsalud.org)
Activates2
- The inflammasome activates a pyroptotic inflammatory cascade. (wikipedia.org)
- Live Orientia, but not heat- or UV-inactivated Orientia, activates the inflammasome through active bacterial uptake and endo/phagosomal maturation. (harvard.edu)
Cytosolic multiprotein2
- Inflammasomes are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. (wikipedia.org)
- Inflammasomes are cytosolic multiprotein complexes, whose formation is triggered by sensors of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). (invivogen.com)
Expression6
- More recent studies, however, indicate high levels of inflammasome component expression in epithelial barrier tissues, where they have been shown to represent an important first line of defense. (wikipedia.org)
- RSV inhibited the expression of senescence markers (p53, p16, and p19), inflammasome markers (NLRP3 and Cas1 p20), and nuclear translocation of NF- κ B, hence alleviating infarction area, fibrosis, and cell apoptosis. (hindawi.com)
- Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans. (nature.com)
- Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18R alpha on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. (diva-portal.org)
- We investigated the expression of the NLRP3-inflammasome under high-glucose conditions, assessed the effects of naringin on that process, and further elucidated the role of naringin in the pathogenesis of diabetic kidney disease(DKD). (biomedcentral.com)
- Interest of a Diet Rich in Cajanus Cajan (Pigeon Pea) Associated With a Standardized Exercise Protocol on NLRP3 Inflammasome Expression and Weight Loss in Adult Patients With Severe Obesity. (who.int)
Canonical1
- ASC ( apoptosis-associated speck-like protein containing a CARD domai n, also known as PYCARD) is a protein adaptor important in canonical inflammasome responses [1,2]. (invivogen.com)
Target inflammasome1
- Understanding the involvement of inflammasomes in virus and drug-induced immune activation may help identify molecular markers and CNS immune cells associated with HIV-1 infection or disease progression among substance abuse populations, as well as identify novel therapies to target inflammasome activation or suppression to treat neuroinflammation and immune dysregulation aroused in these processes. (cdc.gov)
Therapeutic8
- These findings implicate endocannabinoids and inflammasome activation in beta cell failure and identify macrophage-expressed CB 1 R as a therapeutic target in T2DM. (nature.com)
- The activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to neuropathic pain and may represent a novel target for pain therapeutic development. (iasp-pain.org)
- In conclusion, we summarize the possible caveats and future perspectives that might provide successful therapeutic approaches against NLRP3 inflammasome for treating or preventing neuropathic pain conditions. (iasp-pain.org)
- The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. (scienceopen.com)
- Therefore, it is important to comprehensively investigate the inflammasome signaling status across various cancers to clarify its clinical and therapeutic significance. (thno.org)
- Six inflammasome clusters were robustly established with distinct molecular, biological, clinical, and therapeutic features. (thno.org)
- Moreover, based on the proposed classification and therapeutic implications, an open website was established to provide tumor patients with comprehensive information on inflammasome signaling. (thno.org)
- These findings highlight the importance of inflammasome evaluation in tumor classification and provide a foundation for improving relevant therapeutic regimens. (thno.org)
Inhibitors1
- Discovering and developing novel small molecule pan-inflammasome inhibitors for treating inflammatory diseases. (immventionthera.com)
NLRP1 and NLRP37
- Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. (scienceopen.com)
- NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. (scienceopen.com)
- Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1 β and IL-18, in primary cortical neurons. (scienceopen.com)
- Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1 β and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. (scienceopen.com)
- IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. (scienceopen.com)
- Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. (scienceopen.com)
- Studies suggest that disruption of NLRP1 and NLRP3 has a major role for these inflammasomes in internal immunity and inflammation as well as metabolic disorders. (bvsalud.org)
Responses1
- The inflammasome governs activation of inflammatory responses, through one of two very important arms of our immune system our innate immune response (and only recently discovered in 2002! (bioindividualnutrition.com)
Therapies1
- We seek to unravel the secrets of inflammasomes - protein complexes at the heart of inflammation and disease - to allow for new therapies to fight human diseases. (inflammasomelab.com)
Chronic4
- Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage. (nature.com)
- The NLRP3 inflammasome mediates inflammation in several chronic diseases by processing the cytokines pro-interleukin (IL)-1β and pro-IL-18. (monash.edu)
- The researches indicated that the abnormal activation of NLRP3 inflammasome was related to the pathogenesis of various autoimmune, chronic inflammatory and metabolic diseases, including gout, atherosclerosis and type 2 diabetes [ 2 - 4 ]. (ijbs.com)
- The scientific objective of this Funding Opportunity Announcement is to encourage research to delineate the role of inflammasomes in the neuropathology produced by acute or chronic drug exposure and HIV infection. (cdc.gov)
Molecular7
- Inflammasome activation is initiated by different kinds of cytosolic pattern recognition receptors (PRRs) that respond to either microbe-derived pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) generated by the host cell. (wikipedia.org)
- This NLRP1 multi-molecular complex was dubbed the 'inflammasome', which spurred much interest in the following years. (wikipedia.org)
- The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. (nih.gov)
- Nerve injury leads to neuronal damage and apoptosis associated with the release of an array of pathogen- or damage-associated molecular patterns to activate inflammasomes. (iasp-pain.org)
- NLRP3 inflammasome can be activated by different stimuli including pathogen associated molecular patterns (PAMPs) and damage associated molecular pattern (DAMPs). (ijbs.com)
- The Inflammasome Lab is a group of researchers led by Professor Kate Schroder at the Institute for Molecular Bioscience, The University of Queensland. (inflammasomelab.com)
- Cryopyrin is involved in the assembly of a molecular complex called an inflammasome, which helps trigger the inflammatory process. (medlineplus.gov)
Cytokines2
- Some of the NLRs also sense nonmicrobial danger signals and form large cytoplasmic complexes called inflammasomes that link the sensing of microbial products and metabolic stress to the proteolytic activation of the proinflammatory cytokines IL-1beta and IL-18. (nih.gov)
- The differences in bioactivity of NiO-NP and CeO2-NP are likely due to NiO-NP facilitating the release of cathepsin B and in turn inflammasome activation generating proinflammatory cytokines. (cdc.gov)
Mitochondrial1
- Manganese caused mitochondrial dysfunction in treated microglial cells and stimulated their release of exosomes containing the inflammasome adaptor protein ASC. (omniprex.com)
Pyrin domain4
- NLR family pyrin domain containing 3 (NLRP3) inflammasomes and peripheral neuropathic pain - Emphasis on microRNAs (miRNAs) as important regulators. (iasp-pain.org)
- Among various inflammasomes, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome senses not only pathogen-derived stimuli, but also senses cellular and homeostatic stress. (manchester.ac.uk)
- The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. (biomedcentral.com)
- The innate immune system is the first line of protection against invading microorganisms, and the pyrin domain-containing-3 (NLRP3) inflammasome is an important component of it. (biomedcentral.com)
Oxidative stress1
- In non-segmental vitiligo, early factors include activation of innate immunity, inflammasome activation, oxidative stress, and loss of melanocyte adhesion. (medscape.com)
Inhibits1
- Detecting of inflammasome assembly in post-mortem COVID-19 lungs, we asked whether and how metformin inhibits inflammasome activation while exerting its anti-inflammatory effect. (lu.se)
Proteins2
- In addition to NLR proteins, other PRRs can form inflammasomes. (wikipedia.org)
- Inflammasome is a complex composed of several proteins and an important part of the natural immune system. (ijbs.com)
Dysfunction1
- Dysfunction of the inflammasome can lead to exacerbated inflammation in several human conditions. (frontiersin.org)
NLRs2
- PRRs involved in inflammasomes comprise NLRs (nucleotide-binding oligomerization domain and leucine-rich repeat-containing receptors) as well as AIM2 (absent in melanoma 2), IFI16 (IFN-inducible protein 16) as well as pyrin. (wikipedia.org)
- In this review, we discuss the role of NLRs, and in particular the inflammasomes, in the recognition of microbial and danger components and the role they play in health and disease. (nih.gov)
Stimuli1
- The first stimuli, which is mediated by proinflammatory pathways, such as toll like receptor (TLR)-mediated activation of nuclear factor-kB (NF-kB), promotes the upregulation of the components of the inflammasome. (ijbs.com)
Pathogenesis2
- Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. (diva-portal.org)
- This systematic review provides an up-to-date evaluation of our current understanding of the roles of inflammasomes in the pathogenesis of T2D and its complications . (bvsalud.org)
Bacterial1
- Completed and published a study demonstrating the first bacterial effector molecule that can inhibit Pyrin inflammasomes. (ntnu.edu)
Inducers1
- The functionality of THP1 ASC-GFP cells has been tested using inflammasome inducers, such as the microbial toxin nigericin and transfected poly(dA:dT). (invivogen.com)
Kate Schroder1
- While no NLRP3-targeting drugs have hit the market just yet, "the science is unequivocal," says Kate Schroder, an inflammasome researcher at the University of Queensland in Australia and one of the co-inventors on inflammasome inhibitor patents originally licensed to the Ireland-based company Inflazome (since acquired by Roche). (the-scientist.com)
Mice2
- In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. (medrxiv.org)
- The treatment of aging mice with NLRP3 inflammasome inhibitor will be needed. (biomedcentral.com)
Triggers2
- ABOVE: Once activated, the NLRP3 inflammasome (illustrated) triggers a suite of pathways that may play an important role in many different diseases. (the-scientist.com)
- Therefore, live O. tsutsugamushi triggers ASC inflammasome activation leading to IL-1β production, which is a critical innate immune response for effective host defense. (harvard.edu)
AIM22
- classified an inflammasome of the PYHIN (pyrin and HIN domain-containing protein) family, termed absent in melanoma 2 (AIM2) which assembles upon sensing foreign cytoplasmic double-stranded DNA (dsDNA). (wikipedia.org)
- TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. (diva-portal.org)
Promotes1
- Preclinical models also showed that in addition to disrupting the formation of the NLRP3 inflammasome, HT-6184 promotes the disassembly of the inflammasome once activated. (wkrg.com)
Regulate1
- Therefore, NLRP3 inflammasome can regulate the immune response of the body and strictly control the inflammatory reaction in the pathophysiological process. (ijbs.com)
Mechanism4
- Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. (nature.com)
- The Inflammasome: More Than a Protective Innate Immune Mechanism. (ox.ac.uk)
- Recent studies indicated that H 2 S played anti-inflammatory and pro-inflammatory roles in many diseases through influencing NLRP3 inflammasome, but its mechanism was not fully understood. (ijbs.com)
- Therefore, results from this study suggest that ENM-induced ROS is not likely a mechanism of inflammasome activation. (cdc.gov)
Findings3
- Our findings revealed that RSV protected against ischemia-induced mouse heart injury in vivo and hypoxia-induced NRCM injury in vitro via regulating Sirt1/p53-mediated cell senescence and inhibiting NLRP3-mediated inflammasome activation. (hindawi.com)
- Taken together, the findings suggested that in Muckle-Wells, inflammasomes made with NLRP3 instead of NLRP1 were constantly forming and could be producing huge amounts of IL-1β, causing the man's illness. (the-scientist.com)
- In the current review, we provide an up-to-date summary of the recent findings on the involvement of NLRP3 inflammasome in modulating neuropathic pain development and maintenance, focusing on peripheral neuropathic conditions. (iasp-pain.org)
Inhibitor1
- However, the selective inhibitor of NLRP3 inflammasome was lacking. (biomedcentral.com)
Anti-inflammatory1
- In this review, we summarized the recent studies on the anti-inflammatory or pro-inflammatory effects of H 2 S on NLRP3 inflammasome in a variety of diseases to provide ideas for the relevant basic research in the future. (ijbs.com)
Autoimmune4
- In the case of dysregulation of inflammasome activation, an assortment of major diseases, such as cancer, autoimmune, metabolic and neurodegenerative diseases may arise. (wikipedia.org)
- Look at the over 800 studies linking inflammasomes to cancer, and over 400 studies linking it to autoimmune disease, as well as heart disease, Alzheimer's disease, Parkinson's disease. (bioindividualnutrition.com)
- In this interview, Susan Owens shares her insight into how oxalate is involved with the inflammasome and autoimmune disease (as well as autism of course). (bioindividualnutrition.com)
- Inflammasomes and Childhood Autoimmune Diseases: A Review of Current Knowledge. (cdc.gov)
Oligomerization1
- Although several types of inflammasomes have been identified so far, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is the most characteristic one [ 1 ]. (ijbs.com)
Senescence1
- The aim of this study was to investigate whether resveratrol (RSV) could ameliorate ischemia- and hypoxia-associated cardiomyocyte apoptosis and injury via inhibiting senescence signaling and inflammasome activation. (hindawi.com)
Biopharma1
- Torreya Capital's Biopharmaceutical Sector Update Market Outlook ranked "Inflammasome Science" as one of the top five biopharma events of 2020. (the-scientist.com)
Complexes called2
- Additionally, inflammasomes can be incorporated into larger cell death-inducing complexes called PANoptosomes, which drive another distinct form of pro-inflammatory cell death called PANoptosis. (wikipedia.org)
- Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. (scienceopen.com)
Regulates1
- report that the inflammasome regulates the balance between erythroid and myeloid differentiation in model systems, providing insights into hematopoietic lineage bias associated with inflammatory conditions. (ox.ac.uk)