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28-496: (Redirected from Il-10 ) Interleukin 10 (Il-10) is an anti-inflammatory cytokine. IL-10 may also refer to: Ilyushin Il-10 , a Soviet aircraft of World War II Interleukin 10 , an anti-inflammatory cytokine Illinois's 10th congressional district Illinois Route 10 [REDACTED] Topics referred to by the same term This disambiguation page lists articles associated with
56-451: A broad range of functions and is involved in a variety of immune and non-immune processes in the body. For example, IL-20 is involved in the process of wound healing , proliferation of epithelial cells , prevention of apoptosis of epithelial cells , regulation of differentiation of keratinocytes during inflammation , the expansion of multipotential hematopoietic progenitor cells , and more. A specific receptor for this cytokine
84-440: A decrease in serum TGFβ. These findings are consistent with the published preclinical immunoncology reports using PEG-rMuIL-10 and with previous findings treating humans with rHuIL-10. These data suggest that while IL-10 can exert immunosuppressive effects in context of bacterial product stimulated myeloid cells, rHuIL-10/PEG-rHuIL-10 treatment of humans is predominantly immunostimulatory. As of 2018 AM0010 (aka pegilodecakin )
112-576: A potent ability to suppress the antigen-presentation capacity of antigen presenting cells; however, it is also stimulatory towards certain T cells (Th2) and mast cells and stimulates B cell maturation and antibody production. IL-10 checks the inducible form of Cyclo-oxygenase, Cyclo-oxygenase-2 (COX-2). Lack of IL-10 has been shown to cause COX activation and resultant Thromboxane receptor activation to cause vascular endothelial and cardiac dysfunctions in mice. Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. IL-10
140-536: A randomized, double blind, placebo controlled Phase II trial. Further investigation of rHuIL-10's effects in humans suggests that rather than inhibiting inflammation, rHuIL-10 is capable of exerting pro-inflammatory effects. Further to these data, a Phase I immunoncology clinical trial is currently being conducted to assess the therapeutic capacity of PEGylated recombinant human IL-10 (PEG-rHuIL-10, AM0010). Consistent with preclinical immunoncology data, investigators report substantial anti-tumor efficacy. Contrary to
168-403: Is a homodimer ; each of its subunits is 178- amino-acid long. IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19 , IL-20 , IL-22 , IL-24 (Mda-7), IL-26 and interferons type-I ( IFN-alpha , -beta, -epsilon, -kappa, -omega), type-II (IFN-gamma) and type-III (IFN-lambda, including IL-28A , IL-28B , IL-29 , and IFNL4 ). In humans, IL-10 is encoded by
196-514: Is a protein that is in humans encoded by the IL20 gene which is located in close proximity to the IL-10 gene on the 1q32 chromosome . IL-20 is a part of an IL-20 subfamily which is a part of a larger IL-10 family . IL-20 subfamily also includes other cytokines , including IL-19 , IL-20, IL-22 , IL-24 , and IL-26 . Members of the cytokine IL-20 subfamily form an important link between
224-476: Is a cytokine with multiple, pleiotropic , effects in immunoregulation and inflammation. It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages . It also enhances B cell survival, proliferation, and antibody production. IL-10 can block NF-κB activity, and is involved in the regulation of the JAK-STAT signaling pathway . Discovered in 1991, IL-10
252-415: Is also associated with bladder cancer . On the other hand, IL-20 is known to prevent tissue damage as a result of chronic inflammation which may reduce the chance of developing cancer . So the role of IL-20 in cancer development is ambiguous and needs to be further explored. IL-20 is an angiogenesis factor and is highly expressed in artery plaques found in patients with atherosclerosis . IL-20
280-544: Is also mediated by GPCRs , such as beta-2 adrenergic and type 2 cannabinoid receptors. The expression of IL-10 is minimal in unstimulated tissues and seems to require triggering by commensal or pathogenic flora. IL-10 expression is tightly regulated at the transcriptional and post-transcriptional level. Extensive IL-10 locus remodeling is observed in monocytes upon stimulation of TLR or Fc receptor pathways. IL-10 induction involves ERK1 / 2 , p38 and NF-κB signalling and transcriptional activation via promoter binding of
308-527: Is an anti- inflammatory cytokine . In humans, interleukin 10 is encoded by the IL10 gene. IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively. The IL-10 protein
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#1732780375619336-552: Is an essential molecular marker of regulatory T ( Treg ) cells. Foxp3 polymorphism (rs3761548) might be involved in cancer progression like gastric cancer through influencing Tregs function and the secretion of immunomodulatory cytokines such as IL-10, IL-35 , and TGF-β . A recent mouse study indicates that IL-10 regulates CD36, a key phagocytosis effector, promoting hematoma clearance after intracerebral hemorrhage. IL-10 deficiency aggravates traumatic brain injury in male but not female mice. Knockout studies in mice suggested
364-471: Is highly upregulated in psoriatic skin . Dysfunctional regulation of IL-20 could lead to uncontrollable wound healing in psoriasis , which could be a contributing factor to the pathogenesis of this disease . Because IL-20 is involved in the promotion of proliferation of epithelial cells it is also linked to the development of cancer . Receptors for IL-20 are very often expressed on tumorous cells of epithelial origin. High expression of IL-20
392-600: Is in phase 3 clinical trials. IL-10 has been shown to interact with Interleukin 10 receptor, alpha subunit . The receptor complex for IL-10 also requires the IL10R2 chain to initiate signalling. This ligand–receptor combination is found in birds and frogs, and is also likely to exist in bony fish. Interleukin 20 50604 58181 ENSG00000162891 ENSMUSG00000026416 Q9NYY1 Q9JKV9 NM_018724 NM_021380 NM_001311091 NP_061194 NP_001298020 NP_067355 Interleukin 20 (IL20)
420-493: Is involved in many stages of rheumatoid arthritis (RA) progression. IL-20 stimulates the secretion of chemokines MCP-1 and IL-8 in synovial fibroblasts , which attract neutrophils and T-cells . IL-20 is also an upstream regulator of TNF-α , IL-1 , and IL-6 , which are involved in the pathogenesis of RA . IL-20 is highly expressed in the synovial fluid of RA patients. Serum levels of IL-20 are not different from those of healthy controls, suggesting that IL-20
448-533: Is involved in the pathogenesis of RA only at local sites of inflammation . Receptors for IL-20 are highly expressed in the synovial membranes of RA patients. Due to the clear association of IL-20 with RA , anti-IL-20 antibody is now in a clinical trial for RA . Anti-IL-20 monoclonal antibodies have been researched as clinical candidates for the treatment or prevention of psoriasis , rheumatoid arthritis , atherosclerosis , osteoporosis , and stroke . The anti-IL-20 antibody has been shown to reduce
476-489: Is linked to the myokines , as exercise provokes an increase in circulating levels of IL-1ra, IL-10, and sTNF-R, suggesting that physical exercise fosters an environment of anti-inflammatory cytokines. Lower levels of IL-10 have been observed in individuals diagnosed with multiple sclerosis when compared to healthy individuals. Due to a decrease in IL-10 levels, TNFα levels are not regulated effectively as IL-10 regulates
504-742: The IL-22 receptor (IL-22RA1) . Both of these receptor variants allow efficient IL-20 signaling. Receptors for IL-20 are expressed in the skin , lungs , ovary , testes , and placenta . IL-20 is mainly produced by myeloid cells such as monocytes , granulocytes , and dendritic cells but can also be produced by keratinocytes and fibroblasts . The expression of IL-20 is stimulated by IL-1β , IL-17 , IL-22 , TNF , and LPS . The main cellular targets of IL-20 are keratinocytes , endothelial cells , and adipocytes . IL-20 has been shown to transduce its signal through signal transducer and activator of transcription 3 ( STAT3 ) in keratinocytes . IL-20 has
532-416: The IL10 gene, which is located on chromosome 1 and comprises five exons , and is primarily produced by monocytes and, to a lesser extent, lymphocytes , namely type-II T helper cells (T H 2), mast cells , CD4 CD25 Foxp3 regulatory T cells , and in a certain subset of activated T cells and B cells . IL-10 can be produced by monocytes upon PD-1 triggering in these cells. IL-10 upregulation
560-460: The TNF-α-converting enzyme. As a result, TNFα levels rise and result in inflammation. TNFα itself induces demyelination of the oligodendroglial via TNF receptor 1, while chronic inflammation has been linked to demyelination of neurons. In melanoma cell lines, IL-10 modulates the surface expression of NKG2D ligands. In addition, Forkhead box protein 3 ( Foxp3 ) as a transcription factor
588-475: The cytotoxic molecules Granzyme B and Perforin and potentiate T cell receptor dependent IFNγ secretion. A study in mice has shown that IL-10 is also produced by mast cells , counteracting the inflammatory effect that these cells have at the site of an allergic reaction . IL-10 is capable of inhibiting synthesis of pro-inflammatory cytokines such as IFN-γ , IL-2 , IL-3 , TNFα and GM-CSF made by cells such as macrophages and Th1 T cells. It also displays
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#1732780375619616-749: The function of this cytokine as an essential immunoregulator in the intestinal tract. and, indeed, patients with Crohn's disease react favorably towards treatment with recombinant interleukin-10-producing bacteria, demonstrating the importance of IL-10 for counteracting the hyperactive immune response in the human body. Due to the data, thousands of patients with a variety of autoimmune diseases were treated with recombinant human IL-10 (rHuIL-10) in clinical trials. Contrary to expectations, rHuIL-10 treatment did not significantly impact disease in patients with Crohn's disease or rheumatoid arthritis. rHuIL-10 treatment initially exhibited promising clinical data in psoriasis, but failed to achieve clinical significance in
644-468: The immune system and epithelial tissues due to the fact that receptors for these cytokines are highly expressed on epithelial cells and are almost exclusively produced by cells of the immune system . IL-20 requires an IL-β-subunit receptor ( IL-20RB ) for signaling, which can form a functional heterodimeric receptor with either the α-subunit of the IL-20 receptor (IL-20RA) or the α1-subunit of
672-467: The reported immunosuppressive effects of IL-10 generated in vitro and in vivo , treatment of cancer patients with PEG-rHuIL-10 elicits a dose titratable induction of the immune stimulatory cytokines IFNγ, IL-18, IL-7, GM-CSF and IL-4. Furthermore, treated patients exhibit fold increases of peripheral CD8+ T cells expressing markers of activation, such as programmed death 1 (PD1)+, lymphocyte activation gene 3 (LAG3)+ and increased Fas Ligand (FasL) and
700-809: The same title formed as a letter–number combination. If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=IL-10&oldid=1047480796 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Interleukin 10 1ILK , 1INR , 1J7V , 1LK3 , 1Y6K , 2ILK , 2H24 3586 16153 ENSG00000136634 ENSMUSG00000016529 P22301 P18893 NM_000572 NM_010548 NP_000563 NP_034678 Interleukin 10 ( IL-10 ), also known as human cytokine synthesis inhibitory factor ( CSIF ),
728-568: The severity of RA in rats , mitigate bone destruction, and more. The anti-IL-20 antibody neutralizes not only IL-20 signaling but also decreases TNF-α , IL-1 , and IL-6 signaling in vivo. A human recombinant monoclonal antibody against IL-20 developed by Novo Nordisk Inc. now entered the IIb phase of a clinical trial . This article incorporates text from the United States National Library of Medicine , which
756-432: The transcription factors NF-κB and AP-1 . IL-10 may autoregulate its expression via a negative feed-back loop involving autocrine stimulation of the IL-10 receptor and inhibition of the p38 signaling pathway. Additionally, IL-10 expression is extensively regulated at the post-transcriptional level, which may involve control of mRNA stability via AU-rich elements and by microRNAs such as let-7 or miR-106. IL-10
784-1127: Was initially reported to suppress cytokine secretion, antigen presentation and CD4+ T cell activation. Further investigation has shown that IL-10 predominantly inhibits lipopolysaccharide (LPS) and bacterial product mediated induction of the pro-inflammatory cytokines TNFα, IL-1β, IL-12, and IFNγ secretion from toll-like receptor (TLR) triggered myeloid lineage cells . Over time a more nuanced picture of IL-10's function has emerged as treatment of tumor-bearing mice has been shown to inhibit tumor metastasis. Additional investigation by multiple laboratories has generated data that further supports IL-10's immunostimulatory capacity in an immunoncology context. Expression of IL-10 from transfected tumor cell lines in IL-10 transgenic mice or dosing with IL-10 leads to control of primary tumor growth and decreased metastatic burden. More recently, PEGylated recombinant murine IL-10 (PEG-rMuIL-10) has been shown to induce IFNγ and CD8+ T cell dependent anti-tumor immunity. More specifically, PEGylated recombinant human IL-10 (PEG-rHuIL-10) has been shown to enhance CD8+ T cell secretion of
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