title: The soluble Interleukin 6 receptor: generation and role in inflammation and cancer.
abstract: Soluble cytokine receptors are frequently found in human serum, most of them possessing antagonistic properties. The Interleukin 6 receptor (IL-6R) is found as a transmembrane protein on hepatocytes and subsets of leukocytes, but soluble isoforms of the IL-6R (sIL-6R) are generated by alternative splicing or by limited proteolysis of the ADisintegrin And Metalloproteinases (ADAM) gene family members ADAM10 and ADAM17. Importantly, the sIL-6R in complex with its ligand Interleukin 6 (IL-6) has agonistic functions and requires cells expressing the signal transducing ß-receptor gp130 but not the membrane-bound IL-6R. We have called this process IL-6 trans-signaling. Naturally occurring isoforms of soluble gp130 (sgp130), which are generated by alternative splicing, are natural inhibitors of IL-6 trans-signaling, leaving IL-6 classic signaling via the membrane-bound IL-6R unaffected. We used recombinant sgp130Fc protein and recently generated transgenic mice expressing high levels of sgp130Fc to discriminate between classic and trans-signaling in vivo, and demonstrated that IL-6 trans-signaling is critically involved in generation and maintenance of several inflammatory and autoimmune diseases including chronic inflammatory bowel disease, rheumatoid arthritis, peritonitis and asthma, as well as inflammation-induced colon cancer.
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Olshausenstraße 40, Kiel, Germany.
authors.forename: Athena
authors.initials: A
authors.lastname: Chalaris
authors.forename: Christoph
authors.initials: C
authors.lastname: Garbers
authors.forename: Björn
authors.initials: B
authors.lastname: Rabe
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scheller
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019947:Receptors, Interleukin-6