Gene location and structure
The ''IL-37'' gene is in the human located on the Chromosome, long chromosome arm of chromosome 2. There has not been found any Homologous gene, homolog gene in mice genome. IL-37 undergoes alternative splicing with 5 different splice variants depending on which of the 6 possible exons are being expressed: IL-37a-e. IL-37b is the largest and most studied one; it shares the beta barrel structure that is spread within the interleukin-1 family.Gene expression
''IL-37a,b,c'' are being Gene expression, expressed in a variety of Tissue (biology), tissues - thymus, lung, Large intestine, colon, uterus, bone marrow. It is produced by immune cells, most of which are relevant to the Inflammation, immune inflammation response. Examples include natural killer cells, activated B cell, B lymphocytes, monocyte, circulating blood monocytes, tissue macrophages, keratinocytes or epithelial cells. Some IL-37 Protein isoform, isoforms are Tissue (biology), tissue specific and have varying lengths depending on which exons are being expressed: IL-37a is found in the brain. The isoform includes exons 3, 4, 5, and 6 and the isoform is 192 amino acids in length IL-37b is found in the kidney, bone marrow, blood, skin, Respiratory tract, respiratory and urogenital tract. Exons 1, 2, 4, 5, and 6 are expressed and the isoform is 218 amino acids in length. IL-37c is found in the heart, and contains exons 1, 2, 5, and 6 for a total amino acid length of 197. IL-37d is found in the bone marrow and includes exons 1, 4, 5, and 6 for a total length of 197. IL-37e is found in the Testicle, testis and includes exons 1, 5, and 6 totaling 157 amino acids.Function
The mechanism of IL-37 functions is still to be elucidated. Known functions of IL-37 include anti-inflammatory effects, tumor suppression, and antimicrobial responses. IL-37 acts intracellulary and extracellulary, classifying the cytokine as dual-function.IL-37 Synthesis
IL-37, similar to other members of the interleukin-1 family, is synthesized by blood monocytes in a precursor form and secreted into the cytoplasm in response to inflammatory signaling. Examples of relevant inflammatory signals include TLR agonists, IL-1β, or TGF-β. Full maturation requires cleavage by Caspase 1, Caspase-1.Immune System Inhibition
IL-37 is known to have immunosuppression properties through two different binding mechanisms: Interaction with IL-18 cell surface receptors - Intracellular IL-37 can be released from cells following necrosis or apoptosis. IL-37 has two similar amino acid residues with Interleukin 18, IL-18, and thus extracellular IL-37 can interact with Interleukin-18 receptor, IL-18 receptor (IL-18R) and co-receptor IL-1 receptor 8 (IL-1R8). The affinity of IL-37b to IL-18R alpha subunit is much lower compared to IL-18. IL-37b interacts with IL18BP, IL-18 binding protein (IL-18BP), that is an antagonist of IL-18. The binding of IL-37b enhances the IL-18BP functions and can upregulate anti-inflammatory signals. Binding to SMAD3 receptor - Mature intracellular IL-37 can form functional complexes with Phosphorylation, phosphorylated or unphosphorylated Mothers against decapentaplegic homolog 3, Smad3,which can be transported to the cell nucleus. Nucleus IL-37 can have a direct inhibition function on the Protein production, expression of proinflammatory cytokines, pro-inflammatory cytokine gene transcription. Affected cytokines include Interleukin 1 beta, IL-1β, Interferon gamma, IFN-γ, Interleukin 6, IL-6, and TNF-α.Tumor-Controlled Expression
IL-37 functions are active at low IL-37 concentrations. Higher concentrations leads to inactivation via dimer formation. Experiments also show that certain cancer strains correspond to changes in IL-37 expression levels. Breast cancer and ovarian cancer are associated with elevated expression of IL-37. Colon Cancer, Colon cancer, lung cancer, Multiple myeloma, Multiple Myeloma, and Liver cancer, Hepatoma Carcinoma were correlated with decreased expression of IL-37 expression in affected areas.See also
* Interleukin-1 family * Interleukin 18 * Interleukin 18 receptor * Interleukin 18 binding protein * Inflammation * CarcinogenesisReferences
Further reading
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* {{Cytokine receptor modulators