3JVF , 6DF3 , 6GG1
31-467: 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
62-564: A tumour suppressing protein. IL-24 appears to control cell survival and proliferation by inducing rapid activation of particular transcription factors called STAT1 and STAT3 . This cytokine is predominantly released by activated monocytes , macrophages and T helper 2 (Th2) cells and acts on skin, lung, and reproductive tissues. IL-24 performs important roles in wound healing, arthritis , psoriasis and cancer . Several studies have shown that cell death occurs in cancer cells/cell lines following exposure to IL-24. The gene for IL-24
93-440: 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 )
124-576: 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
155-536: 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
186-403: 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
217-476: 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
248-531: Is a protein in the interleukin family, a type of cytokine signaling molecule in the immune system. In humans, this protein is encoded by the IL24 gene . IL-24 is a cytokine belonging to the IL-10 family of cytokines that signals through two heterodimeric receptors: IL-20R1 / IL-20R2 and IL-22R1/IL-20R2. This interleukin is also known as melanoma differentiation-associated 7 ( mda-7 ) due to its discovery as
279-578: Is also important in autoimmune diseases such as psoriasis , rheumatoid arthritis or spondyloarthropathy. IL-24 carries its functions through two types of membrane receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2) with simultaneous activation of the JAK/signal transducer and activator of transcription ( STAT ) pathway within their cytoplasmic domains. IL-24 is a type of cytokine that interacts frequently with class 2 cytokine receptors. IL-24 can form IL-20R1/IL-20R2 and IL-22R1/IL-20R2 which are shared with
310-544: 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
341-527: 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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#1732787358007372-552: 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
403-522: Is an important candidate for cancer therapy. IL-24 is able to induce apoptosis via both intracellular and extracellular signaling mechanisms. Secreted IL-24 protein induces a robust expression of endogenous IL-24 and subsequent induction of tumor-specific killing through an ER stress-mediated pathway as well as by ROS production. The ER stress is the initial pathway in IL-24-induced apoptosis. An important question, which remained unresolved,
434-595: Is highly conserved throughout evolution with sequence homology between species including yeast, dog, cat, monkey and cow. It is located on chromosome 1q32-33 in humans along with several other IL-10 cytokine family gene members. IL-24 encompasses seven exons and six introns . The cDNA of IL-24 is 1,718 base pairs in length and encodes a protein of 206 amino acid with a predicted molecular size of ˜24 kDa. IL-24 also contains an IL-10 signature motif at amino acids 101–121 shared by other IL-10 family member cytokines. IL-24 possibly can form functionally active dimers due to
465-683: 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 24 11009 93672 ENSG00000162892 ENSMUSG00000026420 Q13007 Q925S4 NM_001185156 NM_001185157 NM_001185158 NM_006850 NM_181339 NM_053095 NP_001172085 NP_001172086 NP_001172087 NP_006841 NP_444325 Interleukin 24 (IL-24)
496-489: 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
527-408: Is located on chromosome 1 in humans. The structure of IL-24 has been found through crystallization by fusing a flexible linker with a ligand to its two receptors, IL-22R1 and IL-20R2. The structure revealed that there is a lack of disulfides , which is present in most cytokines, and is likely the reason why IL-24 is unstable compared to other interleukins. IL-24 is a secreted protein that
558-643: Is that both of the above hypotheses are correct. IL-24 is able to induce toxic autophagy in cancer cells in vitro and animal models in vivo. Past independent studies have also proven that the cytokine can play a role in inflammation for inflammatory bowel disease, psoriasis, cardiovascular disease, rheumatoid arthritis, tuberculosis, and viral infection. Secondary cytokines that evoke antitumor immune responses are stimulated by IL-24. These secondary cytokines include TNF-α , IFN-gamma , and IL-1 , which induce apoptosis. IL-24 also inhibits cancer by blocking VEGF and TGF-alpha activities through inhibition of Src ,
589-487: Is why IL-24 has the abilities to selectively induce apoptosis in a large spectrum of human cancer-derived cell lines without harming normal cells. One possible reason for this differential killing effect involves inherent biochemical differences between normal and cancer cells (ER stress, ROS production and ceramide ), another possibility is that IL-24 is able to target a molecule that only triggers apoptosis in cancer cells. The third option for this differential killing effect
620-416: 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
651-460: 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
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#1732787358007682-475: 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
713-692: The first rounds of CD8 cell expansion to prevent uncontrolled T cell responses. After the combination of anti-IgM and CD40-L stimulation, B lymphocytes can also induce IL-24 expression. In response to immune cells, non-lymphoid cells such as melanocytes can also produce IL-24. IL-24 is an immunomodulatory cytokine which can also display broad cancer-specific suppressor effects. The tumor suppressor activities of IL-24 include inhibition of angiogenesis , sensitization to chemotherapy , and induction of cancer-specific apoptosis . Given its ubiquitous apoptotic effect on malignant cells, lack of an effect on normal cells, and absence of significant side effects, IL-24
744-749: 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
775-481: The other IL-20SFCs and IL-22. IL-20SFC is an IL-20 subfamily of cytokines which includes IL-19 , IL-20 , and IL-24. They all signal through the common chain that is IL-20R2. Through these two types of membrane receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2), simultaneous activation of the JAK/signal transducer and activator of transcription (STAT) pathway within their cytoplasmic domains. Although it belongs to
806-718: The presence of potential disulfide bonds. Researchers identified a number of splice variants of IL-24 lacking one or more exons. The signal peptide in IL-24 is two times the length as in other related human cytokines (51 amino acids), and the predicted molecular mass of IL-24 monomer is 18.3 kDa. IL-24 functions as a cytokine (at low concentrations). Its normal physiological role is connected with wound healing (In normal skin cells, it suppress keratinocyte proliferation during wound healing ), and protection against diseases caused by bacteria (for example Mycobacterim tuberculosis , Salmonella typhimurium , Pseudomonas aeruginosa ). It
837-467: 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
868-506: The same group of cytokines as IL-10 , it has different effect on the immune system. IL-10 is a suppressive cytokine that suppresses inflammation while also maintaining immunomodulatory functions. Beside the normal physiological roles, IL-24 inhibits tumor growth, invasion, metastasis and angiogenesis . IL-24 can be produced by myeloid cells (in response to microbial products through TLRs ), lymphoid cells , and epithelial cells in response to cytokine stimulation. IL-24 can also dampen
899-809: 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 ),
930-432: 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
961-1127: 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