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Blood, 24 September 2009, Vol. 114, No. 13, pp. 2812-2818. Prepublished online as a Blood First Edition Paper on August 3, 2009; DOI 10.1182/blood-2009-01-200915. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-01-200915v1 114/13/2812    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 Kastl, S. P. Articles by Wojta, J. PubMed PubMed Citation Articles by Kastl, S. P. Articles by Wojta, J. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Thrombin induces the expression of oncostatin M via AP-1 activation in human macrophages: a link between coagulation and inflammation Stefan P. Kastl1,2, Walter S. Speidl1, Katharina M. Katsaros1, Christoph Kaun1, Gersina Rega1, Afshin Assadian3, Georg W. Hagmueller3, Martina Hoeth4, Rainer de Martin4, Yongsheng Ma5, Gerald Maurer1, Kurt Huber6, and Johann Wojta1,2 1 Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria; 2 Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria 3 1st Department of General and Vascular Surgery, Wilhelminenhospital, Vienna, Austria; 4 Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria; 5 Department of Biological Sciences, Idaho State University, Pocatello; and 6 3rd Department of Medicine, Wilhelminenhospital, Vienna, Austria Macrophages as inflammatory cells are involved in the pathogenesis of atherosclerosis that today is recognized as an inflammatory disease. Activation of coagulation leads to the late complication of atherosclerosis, namely atherothrombosis with its clinical manifestations stroke, unstable angina, myocardial infarction, and sudden cardiac death. Thus inflammation and coagulation play fundamental roles in the pathogenesis of atherosclerosis. We show that the coagulation enzyme thrombin up-regulates oncostatin M (OSM), a pleiotropic cytokine implicated in the pathophysiology of vascular disease, in human monocyte-derived macrophages (MDMs) up to 16.8-fold. A similar effect was seen in human peripheral blood monocytes and human plaque macrophages. In MDMs, the effect of thrombin on OSM was abolished by PPACK and mimicked by a PAR-1–specific peptide. Thrombin induced phosphorylation of ERK1/2 and p38 in MDMs. The ERK1/2 inhibitor PD98059 blocked the effect of thrombin on OSM production in MDMs, whereas the p38 inhibitor SB202190 had no effect. Thrombin induced translocation of c-fos and c-jun to the nucleus of MDMs. Using OSM promoter–luciferase reporter constructs transfected into MDMs, we show that a functional AP-1 site is required for promoter activation by thrombin. We present another link between coagulation and inflammation, which could impact on the pathogenesis of atherosclerosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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