• 1997
  • He was the first to identify monocyte chemotactic protein - 1 / CCL2 in 1983, and PTX3 in 1997. (wikipedia.org)
  • In 1997, MyD88 was identified as the cytosolic protein that recruits IRAKs to the cytosolic domains of IL-1 receptors, mediating IL-1's signal transduction to the cytsolic signal cascade. (wikipedia.org)
  • 1997). "The IL-9 receptor gene, located in the Xq/Yq pseudoautosomal region, has an autosomal origin, escapes X inactivation and is expressed from the Y". Hum. (wikipedia.org)
  • inflammatory
  • The type I receptor is primarily responsible for transmitting the inflammatory effects of interleukin-1 (IL-1) while type II receptors may act as a suppressor of IL-1 activity by competing for IL-1 binding. (wikipedia.org)
  • His team demonstrated in 2005 that the chemokine receptor D6 acts as a decoy and scavenger receptor for inflammatory chemokines. (wikipedia.org)
  • This effect has been predominantly attributed to the repression of key inflammatory transcription factors, including AP-1 and NF-κB, and is termed transrepression. (aspetjournals.org)
  • In recent years, interleukin-13 (IL-13) has received much attention because it has been found to play a major role in malignancies and inflammatory diseases including pulmonary asthma ( 4 -7 ). (aacrjournals.org)
  • IL1Ra is secreted by various types of cells including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the pro-inflammatory effect of IL1β. (wikipedia.org)
  • This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. (wikipedia.org)
  • Each of these cell types is found in acute and chronic inflammatory sites in association with expression of E-selectin, thus implicating E-selectin in the recruitment of these cells to such inflammatory sites. (wikipedia.org)
  • Once, in the nucleus, STAT6 heterodimer molecule regulates gene expression of cell types critical to the balance between host immune defense and allergic inflammatory responses such as the development of Th2. (wikipedia.org)
  • In the case of severe trauma, an overwhelming, systemic inflammatory response can result in additional multi-organ damage to the host cells and the development of multi-organ failure (MOF) [ 1 ]. (hindawi.com)
  • The inflammatory response after severe trauma correlates with the severity of injury and is associated with mortality and the development of complications, such as MOF or sepsis [ 2 , 3 ]. (hindawi.com)
  • In 1994, the "danger theory" of the inflammatory response following trauma or infection has been introduced and has meanwhile significantly broadened our understanding of the immune response [ 4 - 6 ]. (hindawi.com)
  • As unique features, HMGB1, IL-1 α , and IL-33 exert dual functions as intracellular transcription factors and as extracellular inflammatory mediators. (hindawi.com)
  • It binds IL1A and IL1B and inhibits their binding to IL1R1, deterring the inflammatory response which is generally promoted by the binding of type 1 interleukins to interleukin receptor 1 type I. Also known as TNFRSF6, the DcR3 receptor is found primarily in human malignant tissues. (wikipedia.org)
  • Aspirin-exacerbated respiratory disease (AERD) is a syndrome in which chronic asthma is accompanied by nonallergic hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs), leading to acute bronchoconstriction and exacerbation of other lower and upper airway symptoms [ 1 , 2 ]. (pubmedcentralcanada.ca)
  • The ability of classical NSAIDs to inhibit prostaglandin synthesis by cyclooxygenase (COX) isozymes, particularly COX-1, is implicated in these acute exacerbations [ 3 ], but it is not known how they activate mast cells, eosinophils, macrophages, epithelium, and other cells to release a range of inflammatory mediators in susceptible subjects. (pubmedcentralcanada.ca)
  • The elicitation of different TLRs/IL-1Rs results in similar signaling cascades due to their homologous TIR motif leading to the activation of mitogen-activated protein kinases (MAPKs) and the IκB kinase (IKK) complex, which initiates a nuclear factor-κB (NF-κB) and AP-1-dependent transcriptional response of pro-inflammatory genes. (wikipedia.org)
  • intracellular
  • But this is not a common feature for all IL-1 family members, since IL-1β and IL-18 precursor forms do not bind their receptors and require proteolytic cleavage by either intracellular caspase-1 or extracellular neutrophilic proteases. (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)
  • Both receptors have a size of 60kDa, are glycosylated (contains covalent attachments and modifications) and G-protein linked, and can cause an increase in intracellular Ca2+ levels. (wikipedia.org)
  • The carboxyl terminus of the receptors is located on the intracellular side of the protein, and is rich in serine and threonine residues (a characteristic of many proteins of the 7-transmembrane G-protein coupled receptor family). (wikipedia.org)
  • E selectin has a cassette structure: an N-terminal, C-type lectin domain, an EGF (epidermal-growth-factor)-like domain, 6 Sushi domain (SCR repeat) units, a transmembrane domain (TM) and an intracellular cytoplasmic tail (cyto). (wikipedia.org)
  • These receptors initiate an intracellular signaling cascade through adaptor proteins, primarily, MyD88. (wikipedia.org)
  • extracellular
  • More particularly, this invention provides isolated human and murine CD40-L polypeptides that bind to the extracellular binding region of a CD40 receptor. (google.com.au)
  • In murine systems, IL-13Rα2 chain is shown to function as a decoy receptor because its extracellular domain is cleaved and the protein is detected in serum and urine ( 31 ). (aacrjournals.org)
  • IL-1α or IL-1β bind first to the first extracellular chain of IL-1RI, that recruits the IL-1 receptor accessory protein (IL-1RAcP), which serves as a coreceptor and is necessary for signal transduction and it is also needed for activation of IL-1RI by IL-18 and IL-33. (wikipedia.org)
  • The amino terminus of the receptors is located on the extracellular side of the protein, and function to determine the binding specificity of ligands to the receptor. (wikipedia.org)
  • IL-1R2 protein also interacts non-productively with the second component of the signalling IL-1 receptor, namely IL-1RAcP, and a complex of the IL-1R2 and IL-1RAcP extracellular domains with interleukin-1 beta has been solved by X-ray crystallography. (wikipedia.org)
  • kinase
  • The C-terminus is a target for phosphorylation and exhibits kinase activity. (wikipedia.org)
  • Interleukin 12 receptor, beta 2 subunit has been shown to interact with Janus kinase 2. (wikipedia.org)
  • The JAK Janus kinase proteins on the cytoplasmic end of the receptors allows for the phosphorylation of STAT6, which then forms an activated homodimer and are transported to the nucleus. (wikipedia.org)
  • VEGFR-1 is a kinase-defective receptor tyrosine kinase that negatively modulates angiogenesis by acting as a decoy receptor. (wikipedia.org)
  • Axl receptor tyrosine kinase has been associated with numerous diseases, most notably metastatic cancer. (wikipedia.org)
  • 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)
  • Two are active kinases, IRAK-1 and IRAK-4, and two are inactive, IRAK-2 and IRAK-M, but all regulate the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. (wikipedia.org)
  • IL-1 stimulates IRAK-4 to the IL-1R complex initiating the Toll/IL-1 receptor signaling cascade upstream of IRAKs, so the deletion of IRAK-1 does not abolish the activation of NF-κB and mitogen-activated protein kinase pathways. (wikipedia.org)
  • IRAKs were first identified in 1994 by Michael Martin and colleagues when they successfully co-precipitated a protein kinase with type I interleukin-1 receptors (IL-1RI) from human T cells. (wikipedia.org)
  • They speculated that this kinase was the link between the T cell's transmembrane IL-1 receptor and the cytosolic signalling pathway's downstream components. (wikipedia.org)
  • The DNA sequence analysis of IRAK's domains revealed many conserved amino acids with the serine/threonine specific protein kinase Pelle in Drosphila, that functions downstream of a Toll receptor. (wikipedia.org)
  • Even cells without over-expressed IL-1 receptors showed kinase activity when exposed to IL-1, and were able to co-precipitate a protein kinase with endogenous IL-1 receptors. (wikipedia.org)
  • Thus the human IL-1 receptor's accessory protein was named Interleukin-1 Receptor-Associated Kinase. (wikipedia.org)
  • The KD is responsible for the kinase activity of IRAK proteins and consists of 12 subdomains. (wikipedia.org)
  • All IRAK KDs have an ATP binding pocket with an invariable lysine residue in subdomain II, however, only IRAK-1 and IRAK-4 have an aspartate residue in the catalytic site of subdomain VI, which is thought to be critical for kinase activity. (wikipedia.org)
  • Furthermore, PMA-induced activation of LFA-1 on DA-ER cells overexpressing wild-type SHIP was dependent on protein kinase C but independent of mitogen-activated protein kinase activation, whereas cytokine-induced activation was independent of protein kinase C and mitogen-activated protein kinase activation but required phosphatidylinositol-3 kinase activation. (jimmunol.org)
  • Furthermore, PMA-induced activation of LFA-1 on cells overexpressing SHIP is regulated by protein kinase C (PKC), whereas erythropoietin (Epo)- or IL-3-induced activation of LFA-1 involves a phosphatidylinositol-3 kinase (PI-3K) regulated pathway. (jimmunol.org)
  • Anti-phospho-mitogen-activated protein kinase (MAPK) Abs were obtained from New England Biolabs (Mississauga, Ontario, Canada), anti-Erk-1-CT Abs were obtained from Upstate Biotechnology (Lake Placid, NY), and anti-Raf-1 Abs were obtained from Santa Cruz Biotechnology (Santa Cruz, CA). The generation of the N-terminal-specific anti-SHIP Ab was described ( 19 ). (jimmunol.org)
  • molecular
  • The notion that endogenous and exogenous molecular patterns can cause a similar host response through the same receptors challenged the model of the immune system discriminating between "self" and "nonself", but could be sufficiently explained by the "danger theory. (hindawi.com)
  • DAMPs share structural and functional similarities with exogenous, conserved microbial surface structures released from invading microorganisms, so-called pathogen-associated molecular patterns (PAMPs), which, like DAMPs, are recognized by a set of receptors, termed pathogen-recognition receptors (PRRs) [ 4 , 11 - 15 ]. (hindawi.com)
  • Wortmannin and PMA were purchased from Sigma (St. Louis, MO), and the fluorescence dye 2′,7′-bis-(2-carboxyethyl)-(and-6)-carboxyfluo-rescein, acetoxymeyhyl ester (BCECF-AM) was obtained from Molecular Probes (Eugene, OR). (jimmunol.org)
  • monocytes
  • Interleukin (IL)-18 is a pleiotropic proinflammatory cytokine produced primarily by monocytes/macrophages lineage, Kupffer cells, and dendritic cells as well as epithelial cells, such as human keratinocytes ( 13 , 14 ). (aacrjournals.org)
  • phosphorylation
  • In Th1 cells, IL-12 signaling through the IL12 receptor leads to the phosphorylation of STAT4 and continued Th1 differentiation. (wikipedia.org)
  • Exposure to NSAIDs is postulated to shunt the shared substrate arachidonic acid from the prostaglandin (cyclooxygenase) pathway to the leukotriene (5-lipoxygenase) pathway, or to reduce production of a prostaglandin, putatively PGE 2 , that normally suppresses leukotriene synthesis via an EP receptor mechanism [ 2 ], possibly via phosphorylation of LTC 4 synthase [ 6 ]. (pubmedcentralcanada.ca)
  • functional
  • An increase in the binding activity of nuclear proteins to the glucocorticoid responsive element was also observed after SCI, demonstrating a functional element of GR activation. (jneurosci.org)
  • PSGL-1 was detected on the surfaces of bone-metastatic prostate tumor cells, suggesting that it may have a functional role in the bone tropism of prostate tumor cells. (wikipedia.org)
  • genes
  • However, clinical utility can be compromised by the development of side effects, many of which are attributed to the ability of the glucocorticoid receptor (GR) to induce the transcription of, or transactivate, certain genes. (aspetjournals.org)
  • 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)
  • The genes for both receptors are located on chromosome 2q35 and are each encoded by a single exon, and are 20 kb apart in distance. (wikipedia.org)
  • The close proximity and location of these two genes on the chromosome suggest that they are derived from the same ancestor sequence. (wikipedia.org)
  • 2002
  • It is estimated that in the year 2002 alone, 205,000 new patients (including 1,500 male) were diagnosed in the United States and about 40,000 patients died from this disease ( 1 ). (aacrjournals.org)
  • 2015. Ashkenazi, Avi (1 June 2002). (wikipedia.org)
  • human
  • 1994). "Expression cloning of a human IL-12 receptor component. (wikipedia.org)
  • This combination approach showed profound antitumor activity against human breast tumors in xenografted immunodeficient mice. (aacrjournals.org)
  • Definition: Interleukin 1 receptor precursor (AA-17 to 552) (human). (patents.com)
  • The amino acids that are identical between mature human IL-1α and mature IL-1β is 22% while it is 26% when comparing IL-1β to IL-1RA and only 18% when comparing IL-1α to IL-1RA. (wikipedia.org)
  • Flow cytometric analysis of cytokine receptors on human Langerhans' cells. (wikipedia.org)
  • 16. The immunostimulatory regimen of claim 1 wherein the type 1 interferon is a human alpha or beta interferon. (google.com.au)
  • 17. The immunostimulatory regimen of claim 2 wherein the type 1 interferon is a human alpha or beta interferon. (google.com.au)
  • 18. The immunostimulatory regimen of claim 3 wherein the type 1 interferon is a human alpha or beta interferon. (google.com.au)
  • 22. The immunostimulatory regimen of claim 1 wherein the CD40 agonistic antibody or fragment is an agonistic chimeric, human, or humanized anti-CD40 antibody or an agonistic CD40 antibody fragment which is selected from a Fab, F(ab′) 2 , Fd, and a Fv. (google.com.au)
  • Labelling of Peripheral-type Benzodiazepine Binding Sites in Human Brain with 3H! (freepatentsonline.com)
  • The three-dimensional structure of the ligand-binding region of human E-selectin has been determined at 2.0 Å resolution in 1994. (wikipedia.org)
  • There are disclosed therapeutic compositions and methods using isolated nucleic acid molecules encoding a human chemokine beta-11 (Ck beta-11) polypeptide and a human leukocyte adhesion inhibitor-1 (LAI-1) polypeptide (previously termed chemokine α1(CKα1 or ckα-1), as well as Ck beta-11 and/or LAI-1. (google.com)
  • There are disclosed therapeutic compositions and methods using isolated nucleic acid molecules encoding a human chemokine beta-11 (Ck beta-11) polypeptide and a human leukocyte adhesion inhibitor-1 (LAI-1) polypeptide (previously termed chemokine α1(CKα1 or ckα-1), as well as Ck beta-11 and/or LAI-1 polypeptides themselves, as are vectors, host cells and recombinant methods for producing the same. (google.com)
  • complex
  • 3. The method according to claim 1 in which the amount of the first complex is in the range of 5 to 49 micrograms. (google.fr)
  • This receptor is a heterodimer receptor complex consisting of alpha IL-4 receptor (IL-4Rα) and alpha Interleukin-13 receptor (IL-13R1). (wikipedia.org)
  • IRAK-M negatively regulates TLR signaling by inhibiting the IRAK-4/IRAK-1 complex The newest described IRAK family member, IRAK-4, has been found to be critical for the recruitment of IRAK-1 and for its activation/degradation. (wikipedia.org)
  • expression
  • The major objective of this study was to determine the level expression of IL-1 ligands system (IL-1α, IL-1β and IL-1RA) in the most common subtypes of ovarian cancer cells compared to endometrial cells. (springer.com)
  • Endometrioid ovarian cancer exhibits an alteration in the expression of IL-1RA, a key protector against tumorogenic effects of IL-1. (springer.com)
  • Interleukin 4 (IL4) is reported to antagonize the activity of interleukin 1 by inducing the expression and release of this cytokine. (wikipedia.org)
  • Although the glucocorticoid receptor (GR) is suggested to mediate MP actions, limited knowledge is available on its expression and possible function after SCI. (jneurosci.org)
  • GR expression sharply increased at 4 hr (22-fold), peaked at 8 hr (56-fold), rapidly declined at 1 d, and returned to the baseline level at and after 3 d. (jneurosci.org)
  • In the present study, we sought to determine the temporal and spatial patterns of GR expression, GRE transcriptional activity, and colocalization of GR and tumor necrosis factor α (TNF-α) after SCI. (jneurosci.org)
  • The production of E-selectin is stimulated by the expression of P-selectin which in turn, is stimulated by tumor necrosis factor α (TNFα), interleukin-1 (IL-1) and lipopolysaccharide (LPS). (wikipedia.org)
  • Here, we show that the expression of a potential glucagon inhibitor, the adenosine A1 receptor (Adora1), is gradually diminished in α-cells of NOD mice, autoantibody-positive (AA + ) and overtly type 1 diabetic (T1D) patients during the progression of disease. (diabetesjournals.org)
  • This activation of LFA-1 by "inside-out signaling" does not require increased expression of LFA-1 on the cell surface or de novo protein synthesis ( 5 , 6 ). (jimmunol.org)
  • ligands
  • Soluble IL-1 ligands were analyzed by ELISA. (springer.com)
  • We demonstrated that IL-1 ligands were expressed by all endometriosis-associated ovarian cancer subtypes and endometrial cells. (springer.com)
  • The role of these two E-selectin ligands in metastasis in vivo is poorly defined and remains to be firmly demonstrated. (wikipedia.org)
  • In cancer cells, CD44, death receptor-3 (DR3), LAMP1, and LAMP2 were identified as E-selectin ligands present on colon cancer cells. (wikipedia.org)
  • precursor
  • All of the members of IL-1 family, except IL-1Ra, are first synthesized as a precursor protein, which means it is synthesized as a long form of a protein which has to be proteolytically cleaved to a shorter, active molecule, which is generally called a mature protein. (wikipedia.org)
  • The similar feature of IL-1α and IL-33 is that their precursor forms can bind to their respective receptor and can activate signal transduction. (wikipedia.org)
  • Definition: interleukin-1 receptor I precursor--chicken. (patents.com)
  • IL-18, like IL-1β, is synthesized as an inactive precursor (pro-IL-18, 24 kDa) and then cleaved by the IL-1β-converting enzyme, caspase-1, into an active 18-kDa mature form and secreted. (aacrjournals.org)
  • inhibitor
  • IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. (wikipedia.org)