• cytokines
  • DM is acknowledged as a low-grade chronic inflammatory state characterized by the over-secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, which reinforce inflammatory signals thus contributing to the development of complications. (frontiersin.org)
  • In this context, interleukin- (IL-) 1 β , one of the most powerful proinflammatory cytokines, is a strong stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that stimulates the osteoclastogenesis. (hindawi.com)
  • In particular, different studies supported the relationship between inflammatory cytokines such as TNF- α , interleukin- (IL-) 6, IL-11, and IL-17, and osteoclast activity [ 7 - 9 ]. (hindawi.com)
  • This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. (wikipedia.org)
  • Interleukin 18 (IL-18), a member of the IL-1 superfamily of cytokines has been demonstrated to be an important mediator of both innate and adaptive immune responses. (biomedcentral.com)
  • They also include the action of proinflammatory cytokines, the production of reactive oxygen species, DNA fragmentation (typical of necroptosis in type 1 diabetic patients), excessive production of islet amyloid polypeptide with the consequent endoplasmic reticulum stress, disruption in autophagy mechanisms, and protein complex formation, such as the inflammasome, capable of increasing oxidative stress produced by mitochondrial damage. (hindawi.com)
  • Among them, the activation of self-reactive lymphocytes and their infiltration in the pancreas, followed by the release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF- α ), which united with its membrane receptor on the PBC, activate intracellular signaling pathways that end in the induction of proapoptotic mechanisms and, in some cases, cell death through necroptosis [ 13 , 14 ]. (hindawi.com)
  • The Interleukin-1 family (IL-1 family) is a group of 11 cytokines, which plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults. (wikipedia.org)
  • IL-1 family is a group of 11 cytokines, which induces a complex network of proinflammatory cytokines and via expression of integrins on leukocytes and endothelial cells, regulates and initiates inflammatory responses. (wikipedia.org)
  • These cytokines interact with homo- or heteromeric receptors, all including the common gp130 subunit (IL6 signaling transducer, (IL6ST)) [ 13 ]. (pubmedcentralcanada.ca)
  • Recently, Sortilin, an intracellular sorting receptor, member of vacuolar protein sorting-10 (Vps10) domain-containing proteins, has been shown to facilitate the signaling of all helical type 1 cytokines which engage the gp130/LIFR beta complex [ 17 ]. (pubmedcentralcanada.ca)
  • Our previous investigations showed that all three epithelial cell lines respond to N. gonorrhoeae by up-regulation of cytokines and adhesion molecules and that these responses are independent of bacterial internalization and IL-1 production ( 10 ). (jimmunol.org)
  • Toll-like receptors were first discovered in Drosophila and trigger the synthesis and secretion of cytokines and activation of other host defense programs that are necessary for both innate or adaptive immune responses. (wikipedia.org)
  • tumor necros
  • Kumar and colleagues ( 21 ) demonstrated that LPS-induced myocardial dysfunction is mediated by tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), although other downstream mediators have been implicated. (physiology.org)
  • The N-terminal DD is related to a motif that was originally defined as the region of similarity between the cytoplasmic tails of the FAS/Apol/CD95 and TNF (tumor necrosis factor) receptors that is required for cytotoxic signaling by the so-called death receptors (Tartaglia et al. (springer.com)
  • Known inducers of NF-κB activity are highly variable and include reactive oxygen species (ROS), tumor necrosis factor alpha (TNFα), interleukin 1-beta (IL-1β), bacterial lipopolysaccharides (LPS), isoproterenol, cocaine, and ionizing radiation. (wikipedia.org)
  • inhibitor
  • The different AGS proteins exhibit selectivity for G protein subunits and present diverse modes of action ranging from promoting GTP binding as a GEF (AGS1 for Gα i ), stabilizing the GDP-bound complex as a guanine nucleotide dissociation inhibitor (AGS3 for Gα i/o ), and interfering with subunit interaction independently of nucleotide exchange (AGS8 with Gβγ). (aspetjournals.org)
  • NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the IKBKG gene. (wikipedia.org)
  • Nuclear factor-κB (NF-κB) is a transcription factor existing in the unstimulated cell as a latent cytoplasmic complex bound to its inhibitor protein I-κB ( 1 , 2 ). (physiology.org)
  • It has been shown that the C-terminal portion of this protein is sufficient for binding and activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF beta, suggesting that this protein may function as a mediator between TGF beta receptors and TAK1. (wikipedia.org)
  • TLR4
  • In the right: TLR4 (Toll like receptor) pathway regulation by TSPO ligands. (frontiersin.org)
  • Compelling genetic data now suggest that TLR4, acting in conjunction with the secreted protein MD-2, is the sole LPS receptor ( 3 , 37 ). (physiology.org)
  • However, they failed to express TLR4 as well as MD2, two essential components of the receptor complex for LPS in phagocytes and endothelial cells. (jimmunol.org)
  • The presence of soluble CD14, a high-affinity receptor for LPS and other bacterial ligands, enhanced the sensitivity of genital tract epithelial cells to both low and high concentrations of bacteria, suggesting that soluble CD14 can act as a coreceptor for non-TLR4 ligands. (jimmunol.org)
  • For example, studies have identified TLR4 as the receptor for the LPS component of Gram-negative bacteria. (wikipedia.org)
  • macrophages
  • IRAK-M is specific to monomyeloic cells (monocytes and macrophages) while the other IRAKs that are ubiquitously expressed. (wikipedia.org)
  • MiRNAs downregulate the expression of certain target genes by binding complementary sequences of their mRNAs and play an important role in the activation of innate immune cells including macrophages 6 and microglia 7 . (jove.com)
  • The basis for the term "interleukin" was to streamline the growing number of biological properties attributed to soluble factors from macrophages and lymphocytes. (wikipedia.org)
  • LIF cytokine is a glycosylated protein (MW of 37-62 kDa depending on its degree of glycosylation) secreted by extraembryonic part of the embryo at the egg cylinder stage as well as by many cell types in adult organs (e.g.: endometrial cells, fibroblasts, hepatocytes, osteoblasts, monocytes, macrophages, T cells) [ 1 , 2 ]. (pubmedcentralcanada.ca)
  • lectin receptors
  • The sensory apparatus that allows detection of infectious microbes has been deciphered in large part, and it is now known that Toll-like receptors, NOD-like receptors, RIG-I-like helicases, C-type lectin receptors, and cytosolic sensors of DNA, most notably cyclic guanosine monophosphate/adenosine monophosphate synthetase, permit recognition of specific molecules of microbial origin. (mhmedical.com)
  • transmembrane
  • Heterotrimeric G proteins, consisting of the guanine nucleotide-binding Gα subunits with GTPase activity and the closely associated Gβ and Gγ subunits, are important signaling components for receptors with seven transmembrane domains (7TMRs). (aspetjournals.org)
  • Unlike CD-14, which lacks a transmembrane signaling domain, TRLs are transmembrane receptors structurally related to Drosophila toll and to human IL-1 receptors ( 32 ). (physiology.org)
  • proteins
  • All IRAK family members are multidomain proteins consisting of a conserved N-terminal Death Domain (DD) and a central kinase domain (KD). (wikipedia.org)
  • The KD is responsible for the kinase activity of IRAK proteins and consists of 12 subdomains. (wikipedia.org)
  • Gα proteins belonging to all 4 subfamilies, including G s , G i , G q , and G 12 are found to play important roles in receptor tyrosine kinase signaling, regulation of oxidant production, development, and cell migration, through physical and functional interaction with proteins other than 7TMRs. (aspetjournals.org)
  • In recent years, novel accessory proteins involved in the activation of G proteins, either by directly influencing GTP binding or through their association with Gα or Gβγ subunits, have been uncovered ( Sato and Ishikawa, 2010 ). (aspetjournals.org)
  • In 1985 two distinct, but distantly related complementary DNAs encoding proteins sharing human IL-1 activity were reported to be isolated from a macrophage cDNA library, thus defining two individual members of the IL-1 family - IL-1α and IL-1β. (wikipedia.org)
  • After the formation of receptor heterodimeric complex which is assembled by IL-1α or IL-1β, IL-1RI and IL-1RAcP, two intracellular adaptor proteins are assembled by conserved cytosolic regions called Toll- and IL-1R-like (TIR) domains. (wikipedia.org)
  • The p50 and p52 proteins have no intrinsic ability to activate transcription and thus have been proposed to act as transcriptional repressors when binding κB elements as homodimers. (wikipedia.org)
  • hormone receptors
  • This would include the expression of hormone receptors, hormone-dependent immune function, and unique genital tract-specific defensins and mucins ( 1 , 2 , 3 , 4 , 5 ). (jimmunol.org)
  • NF-κB is important in regulating cellular responses because it belongs to the category of "rapid-acting" primary transcription factors, i.e., transcription factors that are present in cells in an inactive state and do not require new protein synthesis in order to become activated (other members of this family include transcription factors such as c-Jun, STATs, and nuclear hormone receptors). (wikipedia.org)
  • subunit
  • NBD is a peptide that acts by binding to regulatory subunit NEMO (IKK-γ) thereby preventing it from binding subunits IKK-α and IKK-β and activating the IKK complex. (wikipedia.org)
  • The gp130 common subunit is believed to explain the functional redundancies with several members of the IL-6 family [ 1 ]. (pubmedcentralcanada.ca)
  • Mediators
  • Despite the important role that the genital tract mucosa plays in immune defense, little is known about the mechanism of epithelial cell activation by pathogens and the receptors and secondary mediators involved in this regulated response. (jimmunol.org)
  • retinoic acid
  • Ethanol exposure during development impairs neuronal signaling mechanisms mediated by the N -methyl- d -aspartate (NMDA) receptors, the retinoic acid receptors, and by growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-I), and basic fibroblast growth factor (bFGF). (mdpi.com)
  • novel
  • Over the last years, novel biological drugs have been developed to antagonize the pathophysiological actions of IL-1β. (frontiersin.org)
  • This review will summarize the main experimental and clinical findings obtained with pharmacological IL-1β inhibitors in the context of the cardiovascular complications of DM, and discuss the perspectives of IL-1β inhibitors as novel therapeutic tools for treating these patients. (frontiersin.org)
  • IRAK-1 is a novel inflammation-related marker and a potential target for lung cancer chemopreventive strategies. (pubmedcentralcanada.ca)
  • pathogens
  • The interleukin-1 receptor (IL-1R) associated kinase (IRAK) family plays a crucial role in the protective response to pathogens introduced into the human body by inducing acute inflammation followed by additional adaptive immune responses. (wikipedia.org)
  • The innate immune system is the first line of defense for protecting the host against invading microbial pathogens and involves a number of host defense systems, including chemokine-directed movement of inflammatory cells and pathogen detection via pattern recognition receptors (PRRs) [ 1 - 3 ]. (pubmedcentralcanada.ca)
  • inflammatory
  • The IL-1 family of ligands includes 11 members and among them IL-1 β emerged as the primary therapeutic target for an expanding number of inflammatory conditions. (hindawi.com)
  • signals
  • According to that, they suggested that IL-1F6, IL-1F8 and IL-1F9 should get new names IL-36α, IL-36β and IL-36γ, even though they are encoded by distinct genes, they use the same receptor complex IL-1Rrp2 and coreceptor IL-1RAcP and deliver almost identical signals. (wikipedia.org)
  • Gene
  • The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. (wikipedia.org)
  • Numerous recent in vivo studies using both IL-18-gene-targeted mice and neutralising agents such as anti-IL-18 antibody or IL-18 binding protein, implicate IL-18 in components of host defence and in responses in autoimmune models of disease [ 1 , 4 - 7 ], increasing interest in it as a therapeutic target. (biomedcentral.com)
  • Insulin is a polypeptide hormone formed by 51 amino acids [ 5 ] which once bound with its receptor, mainly expressed in the liver, muscular, and adipose tissue [ 6 ], and regulates a wide number of physiological processes that comprise gene mechanisms such as cellular growth and differentiation, expression of genes that code for enzymes that trigger glycogen, and lipid and protein synthesis. (hindawi.com)
  • Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the MAP3K7IP1 gene. (wikipedia.org)
  • Many bacterial products and stimulation of a wide variety of cell-surface receptors lead to NF-κB activation and fairly rapid changes in gene expression. (wikipedia.org)