Tumor Necrosis Factor Ligand Superfamily Member 15
Tumor Necrosis Factor Ligand Superfamily Member 13
Tumor Necrosis Factor Ligand Superfamily Member 14
Tumor Necrosis Factor-alpha
Receptors, Tumor Necrosis Factor
Ligands
Receptors, Tumor Necrosis Factor, Type I
Growth Differentiation Factor 6
Receptors, Tumor Necrosis Factor, Type II
RNA, Messenger
Necrosis
Receptors, Platelet-Derived Growth Factor
Molecular Sequence Data
Tumor Necrosis Factors
Cytokines
Cells, Cultured
Signal Transduction
Interleukin-1
Amino Acid Sequence
NF-kappa B
Lipopolysaccharides
Platelet-Derived Growth Factor
Interleukin-6
Mice, Inbred C57BL
Apoptosis
Lymphotoxin-alpha
Base Sequence
Interferon-gamma
Gene Expression Regulation
Macrophages
Tumor Necrosis Factor Decoy Receptors
VEGI, a new member of the TNF family activates nuclear factor-kappa B and c-Jun N-terminal kinase and modulates cell growth. (1/68)
Recently a new member of the human tumor necrosis factor (TNF) family named as VEGI was reported. However, very little is known about the biological activities displayed by this cytokine. In this report, we show that in myeloid cells VEGI activated the transcription factor kappa B (NF-kappa B) as determined by the electrophoretic mobility shift assay, induced degradation of I kappa B alpha, and nuclear translocation of p65 subunit of NF-kappa B. VEGI also activated NF-kappa B-dependent reporter gene expression. In addition, VEGI activated c-Jun N-terminal kinase. When examined for growth modulatory effects, VEGI inhibited the proliferation of breast carcinoma (MCF-7), epithelial (HeLa), and myeloid (U-937 and ML-1a) tumor cells; and activated caspase-3 leading to PARP cleavage. VEGI-induced cytotoxicity was potentiated by inhibitors of protein synthesis. VEGI also induced proliferation of normal human foreskin fibroblast cells. The activity of VEGI could neither be neutralized by antibodies against TNF, nor could it compete with TNF binding, indicating that the activity of VEGI is not due to TNF and it binds to a distinct receptor. These results suggest that VEGI, a new member of the TNF family, has a signaling pathway similar to TNF and is most likely a multifunctional cytokine. (+info)Modulation of endothelial cell growth arrest and apoptosis by vascular endothelial growth inhibitor. (2/68)
Vascular endothelial growth inhibitor (VEGI), a new member of the tumor necrosis factor family, is an endothelial cell-specific gene and a potent inhibitor of endothelial cell proliferation, angiogenesis, and tumor growth. We report here that VEGI mediates the following two activities in endothelial cells: early G(1) arrest in G(0)/G(1) cells responding to growth stimuli, and programmed death in proliferating cells. G(0)/G(1)-synchronized bovine aortic endothelial cells were treated with VEGI before and after the onset of the growth cycle. When the cells were stimulated with growth conditions but treated simultaneously with VEGI, a reversible, early-G(1) growth arrest occurred, evidenced by the lack of late G(1) markers such as hyperphosphorylation of the retinoblastoma gene product and upregulation of the c-myc gene. Additionally, VEGI treatment led to inhibition of the activities of cyclin-dependent kinases CDK2, CDK4, and CDK6. In contrast, VEGI treatment of cells that had entered the growth cycle resulted in apoptotic cell death, as evidenced by terminal deoxytransferase labeling of fragmented DNA, caspase 3 activation, and annexin V staining, all of which were lacking in nonproliferating cells treated with VEGI. Additionally, stress-signaling proteins p38 and JNK were not as fully activated by VEGI in quiescent as compared with proliferating populations. These findings suggest a dual role for VEGI, the maintenance of growth arrest and induction of apoptosis, in the modulation of the endothelial cell cycle. (+info)TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. (3/68)
DR3 is a death domain-containing receptor that is upregulated during T cell activation and whose overexpression induces apoptosis and NF-kappaB activation in cell lines. Here we show that an endothelial cell-derived TNF-like factor, TL1A, is a ligand for DR3 and decoy receptor TR6/DcR3 and that its expression is inducible by TNF and IL-1alpha. TL1A induces NF-kappaB activation and apoptosis in DR3-expressing cell lines, while TR6-Fc protein antagonizes these signaling events. Interestingly, in T cells, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines both in vitro and in vivo. Our data suggest that interaction of TL1A with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect. (+info)A novel secreted splice variant of vascular endothelial cell growth inhibitor. (4/68)
Vascular endothelial cell growth inhibitor (VEGI), a member of the tumor necrosis factor (TNF) family, is an endothelial cell-specific inhibitor of angiogenesis. Overexpression by cancer cells of a secretable VEGI fusion protein resulted in abrogation of xenograft tumor progression, but overexpression of full-length VEGI was completely without effect. This finding indicates that secretion is essential for VEGI action. Here we report the identification of two new VEGI isoforms consisting of 251 and 192 amino acid residues. Both isoforms show endothelial cell-specific expression and share a C-terminal 151-residue segment with the previously described VEGI, which comprises 174 residues. The isoforms are generated from a 17 kb human gene by alternative splicing. Their expression is regulated in parallel by inflammatory cytokines TNF-alpha and interferon-gamma. VEGI-251, the most abundant isoform, contains a putative secretion signal. VEGI protein is detected in conditioned media of endothelial cells and VEGI-251-transfected mammalian cells. Overexpression of VEGI-251 in endothelial cells causes dose-dependent cell death. VEGI-251-transfected cancer cells form xenograft tumors of reduced growth rate and microvessel density compared with tumors of empty vector transfectants. These findings support the view that endothelial cell-secreted VEGI may function as an autocrine inhibitor of angiogenesis and a naturally existing modulator of vascular homeostasis. (+info)TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells. (5/68)
We recently identified TL1A, an endothelium-derived T cell costimulator and a ligand for tumor necrosis factor receptor superfamily members DR3 and decoy receptor 3. To elucidate the signaling events triggered by TL1A-DR3 interaction and to understand the molecular mechanisms regulating DR3-mediated apoptosis, we have studied the effect of TL1A and an agonistic DR3 monoclonal antibody in human erythroleukemic TF-1 cells, which express DR3 endogenously. TL1A induced the formation of a DR3 signaling complex containing TRADD, TRAF2, and RIP and activated the NF-kappaB and the ERK, JNK, and p38 mitogen-activated protein kinase pathways. However, TL1A or an agonistic DR3 monoclonal antibody did not induce apoptosis in these cells nor were there detectable levels of FADD or procaspase-8 seen in the signaling complex. Interestingly, DR3-mediated apoptosis was induced in TF-1 cells in the presence of a NF-kappaB pathway-specific inhibitor but not in the presence of mitogen-activated protein kinase inhibitors, either alone or in combination, suggesting that DR3-induced NF-kappaB activation was responsible for resistance to apoptosis in these cells. Consistent with this, we found that TL1A significantly increased the production of c-IAP2, a known NF-kappaB-dependent anti-apoptotic protein, and that the NF-kappaB inhibitor or cycloheximide prevented its synthesis. Furthermore, inhibition of c-IAP2 production by RNA interference significantly sensitized TF-1 cells to TL1A-induced apoptosis. Our study identifies a molecular mechanism by which TL1A and DR3 regulate cell fate in TF-1 cells. (+info)Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. (6/68)
TL1A is a novel TNF-like factor that acts as a costimulator of IFN-gamma secretion through binding to the death domain-containing receptor, DR3. The aim of this study was to test the hypothesis that TL1A may play an important role in inflammatory bowel disease (IBD) by functioning as a Th1-polarizing cytokine. The expression, cellular localization, and functional activity of TL1A and DR3 were studied in intestinal tissue specimens as well as isolated lamina propria mononuclear cells from IBD patients and controls. TL1A mRNA and protein expression was up-regulated in IBD, particularly in involved areas of Crohn's disease (CD; p < 0.03 vs control). TL1A production was localized to the intestinal lamina propria in macrophages and CD4(+) and CD8(+) lymphocytes from CD patients as well as in plasma cells from ulcerative colitis patients. The amount of TL1A protein and the number of TL1A-positive cells correlated with the severity of inflammation, most significantly in CD. Increased numbers of immunoreactive DR3-positive T lymphocytes were detected in the intestinal lamina propria from IBD patients. Addition of recombinant human TL1A to cultures of PHA-stimulated lamina propria mononuclear from CD patients significantly augmented IFN-gamma production by 4-fold, whereas a minimal effect was observed in control patients. Our study provides evidence for the first time that the novel cytokine TL1A may play an important role in a Th1-mediated disease such as CD. (+info)Soluble decoy receptor 3 induces angiogenesis by neutralization of TL1A, a cytokine belonging to tumor necrosis factor superfamily and exhibiting angiostatic action. (7/68)
TL1A is a member of the tumor necrosis factor superfamily and plays an important role in regulating endothelial cell apoptosis. A previous study shows TL1A is able to interact with death receptor 3 and decoy receptor 3 (DcR3). Here, we demonstrate that DcR3 is able to induce angiogenesis in human umbilical vein endothelial cells (HUVECs). DcR3 promotes HUVEC proliferation and migration and up-regulates matrix metalloproteinase-2 mRNA expression and enzyme activity. Furthermore, DcR3 enhances EC differentiation into cord vascular-like structures in vitro, as well as neovascularization in vivo. The effects of DcR3 on HUVECs are also mimicked by anti-TL1A and antideath receptor 3 antibodies. In contrast, human aortic endothelial cells, which do not express TL1A, are not responsive to DcR3 treatment, including cell proliferation, migration, and angiogenic differentiation. These data demonstrate DcR3 might not only help tumor cells to escape immune surveillance but also induce angiogenesis by blocking TL1A action in endothelial cells. The pathological role of DcR3 in promoting cancer progress raises the possibility to target DcR3 for antiangiogenic therapy in the future. (+info)Effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenoviruses on antiangiogenesis. (8/68)
AIM: To investigate the inhibitory effects of endostatin-vascular endothelial growth inhibitor (VEGI151) recombinant adenoviruses on neovascularization. METHODS: We used recombinant adenoviruses to treat human vascular endothelial cell line ECV304, human hepatocellular carcinoma cell line HepG2, and murine fibroblast cell line L929, in order to study the chimeric gene expression in these cell lines. Chick choriallantic membrane (CAM) model, rabbit inflammatory corneal neovascularization (CNV) model, and liver cancer-bearing nude mice model were employed to investigate the negative biological effect of fusion molecules on neovascularization in vivo. RESULTS: Western blot showed that the molecular weight of fusion protein was about 41 kD after infection of ECV304, HepG2 and L929 cells with supernatant of AdhENDO-VEGI151. The fusion protein showed a specific inhibitory effect on the proliferation of ECV304 cells, but no inhibitory effect on the growth of HepG2 and L929 cells (F=13112.13, P=0.0001). In the chick choriallantic membrane (CAM) assay, the expressed fusion protein significantly inhibited neovascularization. Rabbit inflammatory corneal neovascularization (CNV) induced by intrastromal sutures resulted in a uniform neovascular response. In this model, direct subconjunctival injection of AdhENDO-VEGI151 expressed the fusion protein in vivo and suppressed the development of CNV. Topical application of AdhENDO-VEGI151 led to a significant suppression of CNV (F=1413.11, P=0.0001), as compared with the control group of AdLacZ. Immunohistochemical staining showed the fusion protein dominantly expressed in corneal epithelium. Compared with the control group of AdLacZ (4075.9+/-1849.9 mm(3)), the average tumor size of group AdhENDO-VEGI151 reduced in size (487.7+/-241.2 mm(3)) (F=14.80, P=0.0085), with an inhibition rate of 88.03%. Immunohistochemical staining showed the adenoviruses carried the fusion gene expressed on liver cancer cell membrane. MVD decreased more significantly in treated mice (30.75+/-3.31%) than in AdLacZ control (50.25+/-8.65%) (F=17.72, P=0.0056) with an inhibition rate of 39%. CONCLUSION: Fusion protein expressed by recombinant adenoviruses has a significant inhibitory effect on neovascularization. (+info)Tumor Necrosis Factor Ligand Superfamily Member 15 (TNFSF15) is a type II transmembrane protein that belongs to the tumor necrosis factor (TNF) ligand superfamily. It is also known as vascular endothelial growth inhibitor (VEGI), and it plays a role in regulating immune responses, inflammation, and angiogenesis.
TNFSF15 binds to its receptor, TNFRSF25 (also known as DR3 or APO-3), which is expressed on the surface of various cells including T cells, B cells, and dendritic cells. The binding of TNFSF15 to TNFRSF25 leads to the activation of several signaling pathways, including the nuclear factor kappa B (NF-κB) pathway, which regulates the expression of genes involved in immune responses and inflammation.
TNFSF15 has been shown to have both pro-inflammatory and anti-inflammatory effects, depending on the context. It can promote the activation and survival of T cells, as well as the production of cytokines and chemokines that contribute to inflammation. On the other hand, it can also inhibit angiogenesis and tumor growth by inducing apoptosis in endothelial cells and reducing the expression of pro-angiogenic factors.
Abnormalities in TNFSF15 have been implicated in several diseases, including inflammatory bowel disease, rheumatoid arthritis, psoriasis, and cancer. Therefore, TNFSF15 is a potential target for the development of therapies for these conditions.
Tumor Necrosis Factor Ligand Superfamily Member 13 (TNFSF13), also known as APRIL (A Proliferation-Inducing Ligand), is a type II transmembrane protein and a member of the tumor necrosis factor (TNF) ligand superfamily. It plays a crucial role in the immune system, particularly in the activation, proliferation, and differentiation of B cells, which are key players in the humoral immune response.
TNFSF13 is expressed by various cell types, including macrophages, dendritic cells, and neutrophils. It binds to two receptors: TACI (Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor) and BCMA (B-cell Maturation Antigen), which are primarily found on the surface of B cells. The interaction between TNFSF13 and its receptors promotes the survival, proliferation, and differentiation of B cells into plasma cells, ultimately leading to increased antibody production.
Dysregulation of TNFSF13 has been implicated in several autoimmune and inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and multiple sclerosis (MS). Therefore, targeting this molecule or its signaling pathways has been a focus of research for the development of novel therapeutic strategies in these conditions.
Tumor Necrosis Factor Ligand Superfamily Member 14 (TNFSF14), also known as HVEM (Herpesvirus Entry Mediator) Ligand or Lymphotoxin-like, Inhibitory or Secreting Factor (LIGHT), is a type II transmembrane protein and a member of the Tumor Necrosis Factor (TNF) ligand superfamily. It plays a crucial role in immune cell communication and regulation of inflammatory responses.
TNFSF14 can exist as both a membrane-bound form and a soluble form, produced through proteolytic cleavage or alternative splicing. The protein interacts with two receptors: HVEM (TNFRSF14) and Lymphotoxin β Receptor (LTβR). Depending on the receptor it binds to, TNFSF14 can have either costimulatory or inhibitory effects on immune cell functions.
The binding of TNFSF14 to HVEM promotes the activation and proliferation of T cells, enhances the cytotoxic activity of natural killer (NK) cells, and contributes to the development and maintenance of secondary lymphoid organs. In contrast, the interaction between TNFSF14 and LTβR primarily induces the formation and remodeling of tertiary lymphoid structures in peripheral tissues during inflammation or infection.
Dysregulation of TNFSF14 has been implicated in various pathological conditions, including autoimmune diseases, chronic inflammation, and cancer. Therefore, targeting this molecule and its signaling pathways is an area of interest for developing novel therapeutic strategies to treat these disorders.
Tumor Necrosis Factor-alpha (TNF-α) is a cytokine, a type of small signaling protein involved in immune response and inflammation. It is primarily produced by activated macrophages, although other cell types such as T-cells, natural killer cells, and mast cells can also produce it.
TNF-α plays a crucial role in the body's defense against infection and tissue injury by mediating inflammatory responses, activating immune cells, and inducing apoptosis (programmed cell death) in certain types of cells. It does this by binding to its receptors, TNFR1 and TNFR2, which are found on the surface of many cell types.
In addition to its role in the immune response, TNF-α has been implicated in the pathogenesis of several diseases, including autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, as well as cancer, where it can promote tumor growth and metastasis.
Therapeutic agents that target TNF-α, such as infliximab, adalimumab, and etanercept, have been developed to treat these conditions. However, these drugs can also increase the risk of infections and other side effects, so their use must be carefully monitored.
Tumor Necrosis Factor (TNF) Receptors are cell surface receptors that bind to tumor necrosis factor cytokines. They play crucial roles in the regulation of a variety of immune cell functions, including inflammation, immunity, and cell survival or death (apoptosis).
There are two major types of TNF receptors: TNFR1 (also known as p55 or CD120a) and TNFR2 (also known as p75 or CD120b). TNFR1 is widely expressed in most tissues, while TNFR2 has a more restricted expression pattern and is mainly found on immune cells.
TNF receptors have an intracellular domain called the death domain, which can trigger signaling pathways leading to apoptosis when activated by TNF ligands. However, they can also activate other signaling pathways that promote cell survival, differentiation, and inflammation. Dysregulation of TNF receptor signaling has been implicated in various diseases, including cancer, autoimmune disorders, and neurodegenerative conditions.
A ligand, in the context of biochemistry and medicine, is a molecule that binds to a specific site on a protein or a larger biomolecule, such as an enzyme or a receptor. This binding interaction can modify the function or activity of the target protein, either activating it or inhibiting it. Ligands can be small molecules, like hormones or neurotransmitters, or larger structures, like antibodies. The study of ligand-protein interactions is crucial for understanding cellular processes and developing drugs, as many therapeutic compounds function by binding to specific targets within the body.
Tumor Necrosis Factor Receptor 1 (TNFR1), also known as p55 or CD120a, is a type I transmembrane protein that belongs to the tumor necrosis factor receptor superfamily. It is widely expressed in various tissues and cells, including immune cells, endothelial cells, and fibroblasts. TNFR1 plays a crucial role in regulating inflammation, immunity, cell survival, differentiation, and apoptosis (programmed cell death).
TNFR1 is activated by its ligand, Tumor Necrosis Factor-alpha (TNF-α), which is a potent proinflammatory cytokine produced mainly by activated macrophages and monocytes. Upon binding of TNF-α to TNFR1, a series of intracellular signaling events are initiated through the recruitment of adaptor proteins, such as TNF receptor-associated death domain (TRADD), receptor-interacting protein kinase 1 (RIPK1), and TNF receptor-associated factor 2 (TRAF2). These interactions lead to the activation of several downstream signaling pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), which ultimately regulate gene expression and cellular responses.
TNFR1 has been implicated in various physiological and pathological processes, such as inflammation, infection, autoimmunity, cancer, and neurodegenerative disorders. Dysregulation of TNFR1 signaling can contribute to the development and progression of several diseases, making it an attractive target for therapeutic interventions.
Growth Differentiation Factor 6 (GDF6) is a member of the transforming growth factor-beta (TGF-β) superfamily, which plays crucial roles in various biological processes such as cell growth, differentiation, and development. Specifically, GDF6 is involved in the regulation of skeletal development, joint formation, and limb morphogenesis. It has been shown to inhibit chondrogenic differentiation and promote osteogenic differentiation during bone development. Genetic variations in the GDF6 gene have been associated with certain musculoskeletal disorders, such as osteoarthritis and joint laxity.
Tumor Necrosis Factor (TNF) Receptor II, also known as TNFRSF1B or CD120b, is a type of receptor that binds to the TNF-alpha cytokine and plays a crucial role in the immune system. It is a transmembrane protein mainly expressed on the surface of various cells including immune cells, fibroblasts, and endothelial cells.
The activation of TNFRII by TNF-alpha leads to the initiation of intracellular signaling pathways that regulate inflammatory responses, cell survival, differentiation, and apoptosis (programmed cell death). Dysregulation of this receptor's function has been implicated in several pathological conditions such as autoimmune diseases, cancer, and neurodegenerative disorders.
TNFRII is a member of the TNF receptor superfamily (TNFRSF) and consists of an extracellular domain containing multiple cysteine-rich motifs that facilitate ligand binding, a transmembrane domain, and an intracellular domain responsible for signal transduction. Upon ligand binding, TNFRII forms complexes with various adaptor proteins to activate downstream signaling cascades, ultimately leading to the activation of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and other signaling molecules.
In summary, Tumor Necrosis Factor Receptor II is a key regulator of immune responses and cell fate decisions, with its dysregulation contributing to various pathological conditions.
Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.
Necrosis is the premature death of cells or tissues due to damage or injury, such as from infection, trauma, infarction (lack of blood supply), or toxic substances. It's a pathological process that results in the uncontrolled and passive degradation of cellular components, ultimately leading to the release of intracellular contents into the extracellular space. This can cause local inflammation and may lead to further tissue damage if not treated promptly.
There are different types of necrosis, including coagulative, liquefactive, caseous, fat, fibrinoid, and gangrenous necrosis, each with distinct histological features depending on the underlying cause and the affected tissues or organs.
Platelet-derived growth factor (PDGF) receptors are a group of tyrosine kinase receptors found on the surface of various cells, including fibroblasts, smooth muscle cells, and glial cells. These receptors bind to PDGFs, which are growth factors released by platelets during wound healing and blood vessel formation. Activation of PDGF receptors triggers a cascade of intracellular signaling events that promote cell proliferation, migration, and survival, contributing to the regulation of tissue repair, angiogenesis, and tumor growth. Abnormalities in PDGF signaling have been implicated in several diseases, including cancer, fibrosis, and atherosclerosis.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
Tumor Necrosis Factor (TNF) is a type of cytokine, which is a category of proteins that are crucial to cell signaling. TNF plays a significant role in the body's immune response and inflammation process. Specifically, it's primarily produced by activated macrophages as a defensive response against infection, but it can also be produced by other cells such as T-cells and NK cells.
TNF has two types of receptors, TNFR1 and TNFR2, through which it exerts its biological effects. These effects include:
1. Activation of immune cells: TNF helps in the activation of other inflammatory cells like more macrophages and stimulates the release of other cytokines.
2. Cell survival or death: Depending on the context, TNF can promote cell survival or induce programmed cell death (apoptosis), particularly in cancer cells.
3. Fever and acute phase response: TNF is one of the mediators that cause fever and the acute phase reaction during an infection.
The term 'Tumor Necrosis Factor' comes from its historical discovery where it was noted to cause necrosis (death) of tumor cells in certain conditions, although this is not its primary function in the body. Overproduction or dysregulation of TNF has been implicated in several diseases such as rheumatoid arthritis, inflammatory bowel disease, and some types of cancer.
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.
"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.
Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.
It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.
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.
Interleukin-1 (IL-1) is a type of cytokine, which are proteins that play a crucial role in cell signaling. Specifically, IL-1 is a pro-inflammatory cytokine that is involved in the regulation of immune and inflammatory responses in the body. It is produced by various cells, including monocytes, macrophages, and dendritic cells, in response to infection or injury.
IL-1 exists in two forms, IL-1α and IL-1β, which have similar biological activities but are encoded by different genes. Both forms of IL-1 bind to the same receptor, IL-1R, and activate intracellular signaling pathways that lead to the production of other cytokines, chemokines, and inflammatory mediators.
IL-1 has a wide range of biological effects, including fever induction, activation of immune cells, regulation of hematopoiesis (the formation of blood cells), and modulation of bone metabolism. Dysregulation of IL-1 production or activity has been implicated in various inflammatory diseases, such as rheumatoid arthritis, gout, and inflammatory bowel disease. Therefore, IL-1 is an important target for the development of therapies aimed at modulating the immune response and reducing inflammation.
An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.
NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) is a protein complex that plays a crucial role in regulating the immune response to infection and inflammation, as well as in cell survival, differentiation, and proliferation. It is composed of several subunits, including p50, p52, p65 (RelA), c-Rel, and RelB, which can form homodimers or heterodimers that bind to specific DNA sequences called κB sites in the promoter regions of target genes.
Under normal conditions, NF-κB is sequestered in the cytoplasm by inhibitory proteins known as IκBs (inhibitors of κB). However, upon stimulation by various signals such as cytokines, bacterial or viral products, and stress, IκBs are phosphorylated, ubiquitinated, and degraded, leading to the release and activation of NF-κB. Activated NF-κB then translocates to the nucleus, where it binds to κB sites and regulates the expression of target genes involved in inflammation, immunity, cell survival, and proliferation.
Dysregulation of NF-κB signaling has been implicated in various pathological conditions such as cancer, chronic inflammation, autoimmune diseases, and neurodegenerative disorders. Therefore, targeting NF-κB signaling has emerged as a potential therapeutic strategy for the treatment of these diseases.
A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.
Lipopolysaccharides (LPS) are large molecules found in the outer membrane of Gram-negative bacteria. They consist of a hydrophilic polysaccharide called the O-antigen, a core oligosaccharide, and a lipid portion known as Lipid A. The Lipid A component is responsible for the endotoxic activity of LPS, which can trigger a powerful immune response in animals, including humans. This response can lead to symptoms such as fever, inflammation, and septic shock, especially when large amounts of LPS are introduced into the bloodstream.
Platelet-Derived Growth Factor (PDGF) is a dimeric protein with potent mitogenic and chemotactic properties that plays an essential role in wound healing, blood vessel growth, and cellular proliferation and differentiation. It is released from platelets during the process of blood clotting and binds to specific receptors on the surface of target cells, including fibroblasts, smooth muscle cells, and glial cells. PDGF exists in several isoforms, which are generated by alternative splicing of a single gene, and have been implicated in various physiological and pathological processes, such as tissue repair, atherosclerosis, and tumor growth.
Interleukin-6 (IL-6) is a cytokine, a type of protein that plays a crucial role in communication between cells, especially in the immune system. It is produced by various cells including T-cells, B-cells, fibroblasts, and endothelial cells in response to infection, injury, or inflammation.
IL-6 has diverse effects on different cell types. In the immune system, it stimulates the growth and differentiation of B-cells into plasma cells that produce antibodies. It also promotes the activation and survival of T-cells. Moreover, IL-6 plays a role in fever induction by acting on the hypothalamus to raise body temperature during an immune response.
In addition to its functions in the immune system, IL-6 has been implicated in various physiological processes such as hematopoiesis (the formation of blood cells), bone metabolism, and neural development. However, abnormal levels of IL-6 have also been associated with several diseases, including autoimmune disorders, chronic inflammation, and cancer.
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.
Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.
Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.
The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.
Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.
Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).
Lymphotoxin-alpha (LT-alpha), also known as Tumor Necrosis Factor-beta (TNF-beta), is a cytokine that belongs to the TNF superfamily. It is primarily produced by activated CD4+ and CD8+ T cells, and to some extent by B cells, natural killer (NK) cells, and neutrophils. LT-alpha can form homotrimers or heterotrimers with Lymphotoxin-beta (LT-beta), which bind to the LT-beta receptor (LTβR) and herceptin-resistant tumor cells (HRT) on the surface of various cell types, including immune cells, fibroblasts, and endothelial cells.
The activation of the LTβR signaling pathway plays a crucial role in the development and organization of secondary lymphoid organs, such as lymph nodes, Peyer's patches, and spleen. Additionally, LT-alpha has proinflammatory effects, inducing apoptosis in susceptible cells, activating immune cells, and contributing to the pathogenesis of several inflammatory diseases, including rheumatoid arthritis, psoriasis, and Crohn's disease.
A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.
Interferon-gamma (IFN-γ) is a soluble cytokine that is primarily produced by the activation of natural killer (NK) cells and T lymphocytes, especially CD4+ Th1 cells and CD8+ cytotoxic T cells. It plays a crucial role in the regulation of the immune response against viral and intracellular bacterial infections, as well as tumor cells. IFN-γ has several functions, including activating macrophages to enhance their microbicidal activity, increasing the presentation of major histocompatibility complex (MHC) class I and II molecules on antigen-presenting cells, stimulating the proliferation and differentiation of T cells and NK cells, and inducing the production of other cytokines and chemokines. Additionally, IFN-γ has direct antiproliferative effects on certain types of tumor cells and can enhance the cytotoxic activity of immune cells against infected or malignant cells.
A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.
'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.
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.
Membrane glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbone. They are integral components of biological membranes, spanning the lipid bilayer and playing crucial roles in various cellular processes.
The glycosylation of these proteins occurs in the endoplasmic reticulum (ER) and Golgi apparatus during protein folding and trafficking. The attached glycans can vary in structure, length, and composition, which contributes to the diversity of membrane glycoproteins.
Membrane glycoproteins can be classified into two main types based on their orientation within the lipid bilayer:
1. Type I (N-linked): These glycoproteins have a single transmembrane domain and an extracellular N-terminus, where the oligosaccharides are predominantly attached via asparagine residues (Asn-X-Ser/Thr sequon).
2. Type II (C-linked): These glycoproteins possess two transmembrane domains and an intracellular C-terminus, with the oligosaccharides linked to tryptophan residues via a mannose moiety.
Membrane glycoproteins are involved in various cellular functions, such as:
* Cell adhesion and recognition
* Receptor-mediated signal transduction
* Enzymatic catalysis
* Transport of molecules across membranes
* Cell-cell communication
* Immunological responses
Some examples of membrane glycoproteins include cell surface receptors (e.g., growth factor receptors, cytokine receptors), adhesion molecules (e.g., integrins, cadherins), and transporters (e.g., ion channels, ABC transporters).
Tumor Necrosis Factor (TNF) Decoy Receptors are soluble forms of TNF receptors that act as decoy molecules to neutralize the activity of TNF-α, a pro-inflammatory cytokine. They function by binding to TNF-α and preventing it from interacting with its cell surface receptors (TNFR1 and TNFR2), thereby inhibiting the downstream signaling cascades that lead to inflammation and tissue damage.
There are two main types of TNF decoy receptors:
1. TNF Receptor 1 (TNFR1, also known as p55 or p60) - This type of decoy receptor is produced by alternative splicing of the TNFR1 gene and can be found in both membrane-bound and soluble forms. The soluble form of TNFR1 acts as a decoy receptor for TNF-α, preventing it from binding to its cell surface receptors.
2. TNF Receptor 2 (TNFR2, also known as p75 or p80) - This type of decoy receptor is primarily found in the soluble form and is produced by proteolytic cleavage of the membrane-bound TNFR2. Soluble TNFR2 can bind to TNF-α with higher affinity than TNFR1, making it a more effective decoy receptor.
TNF decoy receptors have been implicated in various physiological and pathological processes, including inflammation, immune regulation, and cancer. They are being investigated as potential therapeutic targets for the treatment of various inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis.
Monoclonal antibodies are a type of antibody that are identical because they are produced by a single clone of cells. They are laboratory-produced molecules that act like human antibodies in the immune system. They can be designed to attach to specific proteins found on the surface of cancer cells, making them useful for targeting and treating cancer. Monoclonal antibodies can also be used as a therapy for other diseases, such as autoimmune disorders and inflammatory conditions.
Monoclonal antibodies are produced by fusing a single type of immune cell, called a B cell, with a tumor cell to create a hybrid cell, or hybridoma. This hybrid cell is then able to replicate indefinitely, producing a large number of identical copies of the original antibody. These antibodies can be further modified and engineered to enhance their ability to bind to specific targets, increase their stability, and improve their effectiveness as therapeutic agents.
Monoclonal antibodies have several mechanisms of action in cancer therapy. They can directly kill cancer cells by binding to them and triggering an immune response. They can also block the signals that promote cancer growth and survival. Additionally, monoclonal antibodies can be used to deliver drugs or radiation directly to cancer cells, increasing the effectiveness of these treatments while minimizing their side effects on healthy tissues.
Monoclonal antibodies have become an important tool in modern medicine, with several approved for use in cancer therapy and other diseases. They are continuing to be studied and developed as a promising approach to treating a wide range of medical conditions.
Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.
In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.
Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.
Vascular endothelial growth inhibitor
Denosumab
LIGHT (protein)
CD153
Herpesvirus entry mediator
Death receptor 6
CD27
RANK
TNFSF12
RANKL
CD69
TNFRSF18
P2RX7
CD40 (protein)
Th 9 cell
SIVA1
B-cell activating factor
Urelumab
TRADD
ICAM-1
Leucine zipper
Mothers against decapentaplegic homolog 7
Alkaline phosphatase
Tumor necrosis factor receptor 1
Fas ligand
Interleukin-1 family
Immune checkpoint
CD134
Lymphotoxin beta receptor
Jelly roll fold
Receptors8
- AIM: To evaluate serum levels of selected cytokine receptors in B-cell precursor acute lymphoblastic leukemia (B-ALL) and their association with acknowledged prognostic factors, relapse-free survival (RFS) and overall survival (OS). (bvsalud.org)
- NOTCH1, NOTCH2, NOTCH3 and NOTCH4 are transmembrane receptors that transduce juxtacrine signals of the delta‑like canonical Notch ligand (DLL)1, DLL3, DLL4, jagged canonical Notch ligand (JAG)1 and JAG2. (spandidos-publications.com)
- Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs. (spandidos-publications.com)
- Objective To identify the role of mature nerve growth factor (mNGF), its immature form proNGF and their receptors in arthritis inflammation. (bmj.com)
- This cytokine is a ligand for receptors TNFRSF13B /TACI, TNFRSF17 /BCMA, and TNFRSF13C /BAFF-R. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. (wikidoc.org)
- [4] BAFF is the natural ligand of three unusual tumor necrosis factor receptors named BAFF-R (BR3), TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), and BCMA (B-cell maturation antigen), all of which have differing binding affinities for it. (wikidoc.org)
- All these ligands act as homotrimers (i.e. three of the same molecule) interacting with homotrimeric receptors, [6] although BAFF has been known to be active as either a hetero- or homotrimer (can aggregate into 60-mer depending on the primary structure of the protein). (wikidoc.org)
- The results also suggest constraining a ligand on the surface of a nanoparticle might as general strategy for selectively targeting clustered receptors. (johnshopkins.edu)
TNFSF154
- Vascular endothelial growth inhibitor (VEGI), also known as TNF-like ligand 1A (TL1A) and TNF superfamily member 15 (TNFSF15), is protein that in humans is encoded by the TNFSF15 gene. (wikipedia.org)
- TL1A is a type II transmembrane protein belonging to the TNF superfamily and has been designated TNF superfamily member 15 (TNFSF15). (novusbio.com)
- inflammatory bowel disease: …mutation of a gene called TNFSF15 (tumour necrosis factor ligand superfamily member 15), which is involved in suppressing inflammation, has been identified as an ethnic-specific IBD susceptibility gene. (britannica.com)
- TL1A (TNFSF15), a ligand belonging to the tumor necrosis factor (TNF) family, is expressed predominantly by endothelial cells and monocytes. (enzolifesciences.com)
Apoptosis11
- It can activate both the NF-κB and MAPK signalling pathways, and acts as an autocrine factor to induce apoptosis in endothelial cells. (wikipedia.org)
- TL1, a novel tumor necrosis factor-like cytokine, induces apoptosis in endothelial cells. (wikipedia.org)
- Depending on the cell context, ligation of DR3 by TL1A can trigger one of two signaling pathways, activation of the transcription factor NF-kB, or activation of caspases and apoptosis. (novusbio.com)
- Many members of the TNF superfamily regulate apoptosis and/or immune cell functions, such as T cell co-stimulation, natural killer cell activation, and B cell homeostasis. (rndsystems.com)
- Many of the current efforts regarding anti-cancer drug development are focused on directing tumor cells to undergo apoptosis. (mdpi.com)
- Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential. (uni-muenster.de)
- Sensitization of multidrug resistant human ostesarcoma cells to Apo2 Ligand/TRAIL-induced apoptosis by inhibition of the Akt/PKB kinase. (uni-muenster.de)
- Anticancer agents sensitize osteosarcoma cells to TNF-related apoptosis-inducing ligand downmodulating IAP family proteins. (uni-muenster.de)
- Ionizing radiation enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulations of death receptor 4 (DR4) and death receptor 5 (DR5) in human osteosarcoma cells. (uni-muenster.de)
- Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). (biomedcentral.com)
- to the resistance to cytotoxic therapies indicating that IAPs are important therapeutic targets for cancer treatment [16 17 Among the IAP family members cIAP1 and cIAP2 inhibit apoptosis by suppressing the apoptotic signaling pathway rather than by directly inhibiting caspase activity [18]. (healthweeks.com)
Proliferation-induci3
- Scholars@Duke publication: B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) mediate CD40-independent help by memory CD4 T cells. (duke.edu)
- The goal of this study was to investigate the role of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in alloresponses driven by memory CD4 T cells. (duke.edu)
- [5] TACI binds worst since its affinity is higher for a protein similar to BAFF, called a proliferation-inducing ligand (APRIL). (wikidoc.org)
Protein13
- The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. (wikipedia.org)
- tumour necrosis factor (TNF), a naturally occurring protein that is produced in the human body by the phagocytic cells known as macrophages. (britannica.com)
- The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself. (cusabio.com)
- The protein encoded by this gene is a member of the TNF-receptor superfamily. (wikidoc.org)
- [2] The DR6 is an alpha-helical integral membrane receptor protein that shows evidence that it has something to do with the inhibition of blood vessels forming on tumors which would allow them to grow larger. (wikidoc.org)
- Tumor cells can induce, through exposition of amyloid precursor protein (APP), DR6-mediated endothelial cell necroptosis allowing tumors metastasis. (wikidoc.org)
- [8] APP ( amyloid precursor protein ) is the natural ligand of DR6 and is first cleaved into Aβ and N-APP. (wikidoc.org)
- We further demonstrated that in vitro administration of pro-inflammatory lipopolysaccharide (LPS) significantly upregulated expression levels of CCL2 and CXCL1 as well as phosphorylation (activation) of the stress-associated transcription factor nuclear factor-kappa B (NF-κB) and the mitogen-activated protein kinases (MAPKs) c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 in cultured astrocytes prepared from cerebral cortices of neonatal rats. (researchsquare.com)
- The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. (cancerindex.org)
- B-cell activating factor ( BAFF ) also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFSF13B gene . (wikidoc.org)
- The secreted decoy receptor 3 (DcR3), a soluble protein of the tumor necrosis factor receptor (TNFR) superfamily blocks the action of TL1A. (enzolifesciences.com)
- The N-terminal baculovirus IAP repeat (BIR) domains of IAP family members have been demonstrated to bind to Smac/DIABLO (second mitochondrion-derived activator of caspase) protein which induces rapid proteasomal degradation of cIAPs [27 28 In addition cIAP1/2 also contain an ubiquitin-associated (UBA) domain that binds to polyubiquitin chains [29] and a less well characterized caspase-recruitment domain (CARD) which was found to be an intrinsic inhibitory domain. (healthweeks.com)
- For this purpose, WIN 55,212-2 was injected in pregnant wistar rats from gestation day 5 to 20 and a detailed analysis of the levels of the neurotrophin brain-derived neurotrophic factor (BDNF) as well as of the signaling molecules extracellular signal-regulated kinase (ERK)1/2 and alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) was carried out in adult offspring. (researchgate.net)
TL1A2
- Th17 cell proliferation is promoted by tumor necrosis factor (TNF)-like ligand 1A (TL1A), which binds to death receptor 3 (DR3) expressed on Th17 cells. (nih.gov)
- On activated T cells, TL1A functions specifically via its surface-bound receptor DR3, (a member of the death-domain containing TNF receptor family) to promote cell survival and secretion of proinflammatory cytokines. (enzolifesciences.com)
Antigen1
- Two main advantages of BCMA as an antigen for CAR-T therapy are the potential reduction of on-target/off-tumor toxicity and the lack of antigen-dependent reduction in CAR-T cell expansion [ 16 ]. (biomedcentral.com)
RANKL4
- Bone homeostasis is maintained by the interplay between the receptor activator of nuclear factor kappa-B (RANK), its soluble activation ligand (RANKL), and OPG. (biomedcentral.com)
- As we previously reported, receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL)/RANK signaling on M2 macrophages promotes the production of chemokines and proinflammatory cytokines to maintain the immunosuppressive tumor environment of extramammary Paget's disease (EMPD). (iiarjournals.org)
- Since EMPD is a skin adenocarcinoma of apocrine gland origin that expresses high levels of RANKL and matrix metalloproteinase (MMP) 7, and EMPD is associated with the presence of RANK + M2 macrophages, we hypothesized that tumor-associated macrophages (TAMs) in adenocarcinomas such as PCAC might also express RANKL and MMP7. (iiarjournals.org)
- Conclusion: Our study suggests that the RANKL/RANK pathway contributes to the development and maintenance of the immunosuppressive tumor microenvironment and denosumab may be a promising adjuvant therapy targeting TAMs in cancer of apocrine origin. (iiarjournals.org)
Cyclophilin ligand interactor1
- It is closely associated with B cell-activating factor of the TNF family (BAFF) receptor, transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) [ 14 ]. (biomedcentral.com)
Type II transmembrane2
- Cytokines in the TNF superfamily bind to oligomeric, type I or type II transmembrane proteins that have multiple extracellular cysteine-rich domains. (rndsystems.com)
- CD70, also known as CD27L, is a 50 kD type II transmembrane glycoprotein and member of the tumor necrosis factor superfamily. (biolegend.com)
Cytokine8
- This cytokine is a ligand for receptor TNFRSF25 (death receptor 3) and TNFRSF6B (decoy receptor 3). (wikipedia.org)
- The Periodic Table of Cytokine and Chemokine Families poster includes members of the tumor necrosis factor (TNF) superfamily, and cytokines belonging to the different families of interleukins, interferons, and chemokines. (rndsystems.com)
- Additionally, it is shown whether each cytokine belongs to the beta-trefoil, four helix bundle, or cysteine-knot superfamily and their subfamily designation. (rndsystems.com)
- Moving to the right, the next eight families shown in the poster belong to the four-helix bundle cytokine superfamily. (rndsystems.com)
- This superfamily is further subdivided into the class I and class II cytokine receptor families. (rndsystems.com)
- Ligands for the class I cytokine receptor family include short-chain and long-chain helical cytokines. (rndsystems.com)
- The short-chain helical cytokine family includes members of the common gamma-chain and common beta-chain families of cytokines. (rndsystems.com)
- Ligands for the class II cytokine receptor family includes the IL-10 family cytokines, along with the type I, type II, and type III interferons, which are shown in columns three, four, and nine of the poster. (rndsystems.com)
CD402
- For the quantification of CD40 ligand (CD40L) in Culture Supernatant, Serum, Plasma (EDTA), Plasma (Heparin). (biosensis.com)
- Scientific Background CD40L is the ligand for CD40, a member of the tumour necrosis factor (TNF) receptor superfamily. (biosensis.com)
Microenvironment6
- Intraoperative IL-6 and s-IL-33R values were higher in the RV compared to the periphery, suggesting secretion from the tumor or tumor microenvironment itself. (bvsalud.org)
- Supportive of this is an almost general expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature in the tumor microenvironment. (bvsalud.org)
- Notch signaling cascades crosstalk with fibroblast growth factor and WNT signaling cascades in the tumor microenvironment to maintain cancer stem cells and remodel the tumor microenvironment. (spandidos-publications.com)
- Of these, tumor-associated macrophages (TAMs) and regulatory T-cells (Tregs) create an immunosuppressive microenvironment through various pathways. (iiarjournals.org)
- For example, Paget's cells release soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) into the tumor microenvironment, stimulating RANK + TAMs to produce CCL17, which recruits Tregs into the lesional skin of patients with extramammary Paget's disease (EMPD) ( 11 , 17 ). (iiarjournals.org)
- Accordingly, investigating the characteristics of cancer-related factors is important to determine the immunological background of the tumor microenvironment in each type of skin cancer. (iiarjournals.org)
Promote tumor growth1
- More recent data show that OPG is also produced in breast tumor cells, and that it can promote tumor growth and metastasis [ 5 , 6 ]. (biomedcentral.com)
Soluble1
- A potential disadvantage of BCMA is that soluble BCMA can be released or shed from tumors into the the surrounding tissues and into the circulation. (biomedcentral.com)
Cytokines4
- The four short-chain helix bundle cytokines that signal through class III receptor tyrosine kinases include M-CSF, SCF, Flt-3 Ligand, and IL-34, and are shown in columns four and five of the poster. (rndsystems.com)
- Members of the IL-10 family cytokines have structural similarities and signal through heterodimeric receptor complexes with common subunits. (rndsystems.com)
- These cytokines belong to the cysteine-knot superfamily and bind to members of the IL-17 receptor family. (rndsystems.com)
- OBJECTIVE- Chronic activation of the nuclear factor-κB (NF-κB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. (diabetesjournals.org)
TNFR1
- The mouse monoclonal antibody NGFR5 (originally C34C) recognizes an epitope within ammino acids 1 - 160 of CD271/NGFR, a 75 kDa transmembrane glycoprotein of the TNFR superfamily. (exbio.cz)
Elisa1
- Description: A sandwich quantitative ELISA assay kit for detection of Human Tumor Necrosis Factor Ligand Superfamily, Member 9 (TNFSF9) in samples from serum, plasma, tissue homogenates or other biological fluids. (1elisakits.com)
Serum Levels1
- The free serum levels of this DR6 are heightened with anti-cell death factors in patients that have later stage ovarian cancer. (wikidoc.org)
Differentiation1
- Triggered by its ligands CD271 affects growth, differentiation, migration and death of the nervous system cells. (exbio.cz)
Clinical3
- Phase III clinical trials of Rova‑T for patients with small‑cell lung cancer and a phase III clinical trial of nirogacestat for patients with desmoid tumors are ongoing. (spandidos-publications.com)
- The interaction of PRRSV with the immune system is believed to be of critical importance for defining immunological and clinical outcomes of the infection and, along with other factors, is associated with an inefficient development of the adaptive immunity. (biomedcentral.com)
- Tumor-infiltrating lymphocytes are related to positive clinical prognoses in numerous cancer types. (cancer-genetics.org)
Activates2
- Canonical Notch signaling activates the transcription of BMI1 proto‑oncogene polycomb ring finger, cyclin D1, CD44, cyclin dependent kinase inhibitor 1A, hes family bHLH transcription factor 1, hes related family bHLH transcription factor with YRPW motif 1, MYC, NOTCH3, RE1 silencing transcription factor and transcription factor 7 in a cellular context‑dependent manner, while non‑canonical Notch signaling activates NF‑κB and Rac family small GTPase 1. (spandidos-publications.com)
- Death receptor 6 ( DR6 ), also known as tumor necrosis factor receptor superfamily member 21 ( TNFRSF21 ), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways. (wikidoc.org)
Motif2
- Chemokines such as chemokine C-C motif ligand 2 (CCL2) and chemokine C-X-C motif ligand 1 (CXCL1) are critical signaling factors regulating post-TBI neuroinflammation. (researchsquare.com)
- Immunohistochemical staining of MMP1 and MMP25 as well as chemokine (C-C motif) ligand (CCL) 5 in the lesional skin from five patients with PCAC showed a substantial number of MMP1-bearing cells and MMP25-bearing cells, as well as CCL5-producing cells, that were distributed in the lesional skin. (iiarjournals.org)
Sensitivity1
- A number of studies have suggested that MGMT deficiency is closely related to the sensitivity of brain tumors to alkylating agents ( 4 - 6 ). (aacrjournals.org)
Gene3
- It has been reported that CD70, a B cell costimulatory molecule encoded by the gene TNFSF7 (tumor necrosis factor ligand superfamily member 7), is overexpressed in CD4 + T cells from patients with SLE due to the demethylation of its promoter. (biomedcentral.com)
- CD70, a B cell costimulatory molecule encoded by the TNFSF7 (tumor necrosis factor ligand superfamily member 7) gene [ 21 ], is typically expressed by activated CD4 + T and CD8 + T cells and early B cell progenitors. (biomedcentral.com)
- Gene landscape and correlation between B-cell infiltration and programmed death ligand 1 expression in lung adenocarcinoma patients from The Cancer Genome Atlas data set. (cancer-genetics.org)
Decoy1
- It is the sole known ligand for death receptor 3, and it can also be recognized by decoy receptor 3. (wikipedia.org)
Cells8
- Immunohistochemistry showed general expression of IL-6 (23/24) in both tumor cells and the vasculature (20/23). (bvsalud.org)
- Moreover, s-IL-6R was expressed in tumor cells in 23/24 studied patients. (bvsalud.org)
- Possible mechanisms for overcoming the resistance of HPV-infected tumor cells to anticancer drugs will be discussed. (mdpi.com)
- BCMA, a member of the tumor necrosis factor (TNF) superfamily, is exclusively expressed in a subpopulation of B cells, normal plasma cells, and malignant plasma cells. (biomedcentral.com)
- The 4-1BB receptor (CDw137), a member of the tumor necrosis factor receptor superfamily, has been shown to costimulate the activation of T cells. (rupress.org)
- Among these, Siglec-8 is a CD33-related family member selectively expressed on human mast cells and eosinophils, and at low levels on basophils. (mdpi.com)
- On the other hand, phagosomes are formed when the pathogen is engulfed by macrophages and fuse with lysosomes to release enzymes and toxic substances, resulting in killing or having cytotoxic effects on bacteria and tumor cells. (frontiersin.org)
- Interleukin (IL)-9-producing subset called Th9 cell, Th22 cells which primarily secrete IL-22, IL-13 and tumor necrosis factor- and Th25 cells via producing IL-25 are believed to be important for initiating allergic reactions and developing airway inflammation. (cdc.gov)
CD271
- The ligand of CD70 is CD27. (biolegend.com)
Functions1
- In ex vivo experiments the effects of proNGF differ from those of mNGF, suggesting that the balance of p75NTR and TrkA expression represents a critical factor in regulating mNGF/proNGF functions, determining which intracellular pathways and biological activities are triggered. (bmj.com)
Nuclear1
- Moreover HAX1 regulates the non-canonical Nuclear Factor-κB (NF-κB) signaling pathway by modulating the stability of NF-κB-Inducing Kinase (NIK) which is one of the substrates of cIAPs. (healthweeks.com)
Antibody4
- Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Tumor Necrosis Factor Ligand Superfamily, Member 9 (TNFSF9) in serum, plasma, tissue homogenates and other biological fluids. (1elisakits.com)
- Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Tumor Necrosis Factor Ligand Superfamily, Member 9 (TNFSF9) in samples from serum, plasma, tissue homogenates and other biological fluids with no significant corss-reactivity with analogues from other species. (1elisakits.com)
- Thompson SJ, Schatteman GC, Gown AM, Bothwell M: A monoclonal antibody against nerve growth factor receptor. (exbio.cz)
- Since its discovery in 2000, initial in vitro studies have found that the engagement of Siglec-8 with a monoclonal antibody or with selective polyvalent sialoglycan ligands induced the cell death of eosinophils and inhibited mast cell degranulation. (mdpi.com)
Subunit1
- Members of the common beta-chain family signal through heterodimeric receptor complexes that contain the common beta-chain subunit, while members of the common gamma-chain family signal through heterodimeric or heterotrimeric receptor complexes that contain the common gamma-chain subunit. (rndsystems.com)
Cell1
- All 35 RCC tumors were histologically subtyped as clear cell (CCRCC), papillary or chromophobe. (bvsalud.org)
Extracellular2
- Members of the IL-1 R family contain extracellular Ig-like domains and mediate signaling through an intracellular Toll/IL-1 R (TIR) domain. (rndsystems.com)
- All of the CD3 polypeptide chains (shown in green), except for the ζ (zeta) chains, have extracellular Ig-like domains and are therefore members of the Ig superfamily. (nih.gov)
Family5
- All RNase T2 family members exhibit a conserved α/β core structure. (frontiersin.org)
- In human, RNase T2 is the only identified member of the RNase T2 family ( 4 ). (frontiersin.org)
- On the far left-hand side of the poster, members of the IL-1 family are shown. (rndsystems.com)
- All IL-1 family members share a conserved beta-trefoil structure and bind to members of the IL-1 receptor (IL-1 R) family. (rndsystems.com)
- The causative agent is an enveloped, single-stranded 15-kb positive-sense RNA virus belonging to the Arteriviridae family in the order Nidovirales [ 3 ] known as PRRS virus (PRRSV). (biomedcentral.com)
Proteins1
- Unlike other members of the tumor necrosis factor receptor superfamily of transmembrane proteins, CD271 has unique intracellular domain structure (lacks catalytic activity) and downstream signaling partners. (exbio.cz)
Regulation1
- 1.02E-02), and regulation of TNF superfamily member 15 and miR181. (biomedcentral.com)