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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 (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 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rabe, B. Articles by Scheller, J. Search for Related Content PubMed PubMed Citation Articles by Rabe, B. Articles by Scheller, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 19, 2007 Accepted November 3, 2007 Transgenic blockade of Interleukin-6-trans-signaling abrogates inflammation Bjorn Rabe, Athena Chalaris, Ulrike May, Georg H Waetzig, Dirk Seegert, Anwen S Williams, Simon A Jones, Stefan Rose-John*, and Jurgen Scheller Department of Biochemistry, Christian-Albrechts-University, Kiel, Germany CONARIS Research Institute AG, Kiel, Germany Department of Medical Biochemistry and Immunology, Cardiff University, Cardiff, United Kingdom * Corresponding author; email: rosejohn{at}biochem.uni-kiel.de. The immunoregulatory cytokine Interleukin-6 (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, which 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-trans-signaling. 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? This article has been cited by other articles: M. A. Nowell, A. S. Williams, S. A. Carty, J. Scheller, A. J. Hayes, G. W. Jones, P. J. Richards, S. Slinn, M. Ernst, B. J. Jenkins, et al. Therapeutic Targeting of IL-6 Trans Signaling Counteracts STAT3 Control of Experimental Inflammatory Arthritis J. Immunol., January 1, 2009; 182(1): 613 - 622. [Abstract] [Full Text] [PDF] S. Tenhumberg, G. H. Waetzig, A. Chalaris, B. Rabe, D. Seegert, J. Scheller, S. Rose-John, and J. Grotzinger Structure-guided Optimization of the Interleukin-6 Trans-signaling Antagonist sgp130 J. Biol. Chem., October 3, 2008; 283(40): 27200 - 27207. [Abstract] [Full Text] [PDF] S. Ahmed, H. Marotte, K. Kwan, J. H. Ruth, P. L. Campbell, B. J. Rabquer, A. Pakozdi, and A. E. Koch Epigallocatechin-3-gallate inhibits IL-6 synthesis and suppresses transsignaling by enhancing soluble gp130 production PNAS, September 23, 2008; 105(38): 14692 - 14697. [Abstract] [Full Text] [PDF]

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