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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1021-1028. Prepublished online as a Blood First Edition Paper on November 7, 2007; DOI 10.1182/blood-2007-07-102137. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-07-102137v1 111/3/1021    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Rabe, B. Articles by Scheller, J. PubMed PubMed Citation Articles by Rabe, B. Articles by Scheller, J. Related Collections Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS Transgenic blockade of interleukin 6 transsignaling abrogates inflammation Björn Rabe1, Athena Chalaris1, Ulrike May1, Georg H. Waetzig2, Dirk Seegert2, Anwen S. Williams3, Simon A. Jones3, Stefan Rose-John1, and Jürgen Scheller1 1 Department of Biochemistry, Christian-Albrechts-University, Kiel, Germany; 2 CONARIS Research Institute, Kiel, Germany; and 3 Department of Medical Biochemistry and Immunology, Cardiff University, Cardiff, United Kingdom The immunoregulatory cytokine interleukin6 (IL6) acts in a pro- and anti-inflammatory fashion. Synthesized by myeloid cells, fibroblasts and endothelial cells, IL6 on target cells, binds to the IL6 receptor (IL6R) and signals via complex formation with the ubiquitously expressed gp130 receptor. Paradoxically, most cells that respond to IL6 during inflammatory states do not express the IL6R and are themselves not directly responsive to the cytokine. A naturally occurring soluble form of the IL6R renders all cells responsive to IL6. This alternative signaling process is called IL6 transsignaling. Here we developed a transgenic strategy based on the overexpression of the soluble form of gp130, which specifically blocks all IL6 responses mediated by the soluble IL6R but does not affect IL6 responses via the membrane bound IL6R. In these mice, inflammatory processes are blocked as in IL6–/– mice, strongly arguing for a major role of the soluble IL6R during inflammation in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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