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Sebastian Weise Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany

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Susan Kralisch Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany
Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany

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Grit Sommer Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany

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Ulrike Lossner Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany

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Matthias Bluher Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany

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Michael Stumvoll Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany

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Mathias Fasshauer Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany
Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany

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The adipokine tissue inhibitor of metalloproteinase (TIMP)-1 is upregulated when weight is gained and promotes adipose tissue development. In the present study, the effect of insulin resistance-inducing and proinflammatory interleukin (IL)-1β on TIMP-1 gene expression and secretion was investigated in 3T3-L1 adipocytes. Interestingly, protein secretion and mRNA production of TIMP-1 were significantly stimulated by IL-1β. Thus, IL-1β induced TIMP-1 secretion in a dose-dependent manner with maximal 3.5-fold upregulation seen at 0.67 ng/ml IL-1β relative to untreated cells. Furthermore, TIMP-1 mRNA synthesis was significantly stimulated by IL-1β in a dose-dependent fashion with 2.5-fold induction seen at IL-1β concentrations as low as 0.02 ng/ml and maximal 8.1-fold upregulation found at 20 ng/ml effector. Induction of TIMP-1 mRNA was also time dependent with maximal 9.6-fold upregulation detectable after 8 h of IL-1β treatment. Signaling studies suggested that janus kinase 2 is involved in IL-1β-induced TIMP-1 mRNA expression. Taken together, our results demonstrate that the TIMP-1 expression is selectively upregulated by proinflammatory IL-1β, supporting a direct association between insulin resistance, inflammation, and adipose tissue development in obesity.

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