title: Interleukin-37.
abstract: IL-37 was formerly termed IL-1 family member 7. The cytokine was discovered by in silico research of human databases. Although there are no genes in the databases with an open reading frame for a murine homologue for IL-37, human IL-37 is functional in the mouse. Like others members of the IL-1 family, IL-37 lacks a signal peptide. The precursor form of IL-37 has a caspase-1 site, but the role of caspase-1 in the processing and secretion of IL-37 has not been documented with certainty. IL-37 is similar to IL-1α and IL-33, in that the cytokine is found in the nucleus where, like IL-1α and IL-33, functions in transcription. Translocation of IL-37 to the nucleus likely involves SMAD3, which is a component of the TGFβ anti-inflammatory signaling pathway. Also similar to IL-1α and IL-33, with loss of membrane integrity upon cell death, the IL-37 precursor exits from the cell where it binds to the IL-18 receptor alpha chain. However, this binding results in reduced inflammation. Without a murine form of IL-37, deletion studies were carried out with specific siRNA. In human monocytes deficient in IL-37, LPS and IL-1β induced cytokines increased 2-3 fold, suggesting that endogenous IL-37 serves as a break on inflammation. Indeed, in mice expressing human IL-37, inflammation is reduced in models of LPS shock, chemical colitis, cardiac ischemia and contact dermatitis.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO, USA; Department of Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands. Electronic address: cdinare333@aol.com.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Department of Pediatrics, Dr. von Hauner Children's Hospital Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Bufler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003092:Colitis / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D020382:Interleukin-18 / Q000235:genetics; D053727:Interleukin-18 Receptor alpha Subunit / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology
chemical_list: C508587:IL37 protein, human; D007375:Interleukin-1; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D020033:Protein Isoforms; D020170:Caspase 1