title: The soluble interleukin-6 receptor and related proteins.
abstract: Interleukin-6 is a cytokine involved in the regulation of the immune system and the central nervous system. Interleukin-6 binds to an interleukin-6 receptor, and then associates with a dimer of the ubiquitously expressed gp130 receptor subunit, which initiates intracellular signaling. The interleukin-6 receptor is found in a soluble form, which is generated by proteolytic cleavage and also to a minor extent by translation from an alternatively spliced mRNA. The complex of interleukin-6 bound to the interleukin-6 receptor can stimulate cells, which only express gp130. Such cells are not responsive to interleukin-6 alone. We have for the first time identified the molecular basis of pro-and anti-inflammatory properties of interleukin-6 and we have defined the generation of the soluble IL-6R as a crucial point in the regulation between these two properties. Furthermore, we have deduced a therapeutic principle, which enables us to exclusively block the pro-inflammatory activities of this important cytokine.
authors.affiliation: Department of Biochemistry, Christian-Albrechts-Universität zu Kiel, Germany. Electronic address: rosejohn@biochem.uni-kiel.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D015850:Interleukin-6; D019947:Receptors, Interleukin-6
keywords: ADAM protease; cancer; cytokine; inflammation; receptor; shedding; trans-signaling