Interleukin-6 Signaling Drives Fibrosis in Unresolved Inflammation

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• 作者：Ceri聽A. Fielding ; Gareth聽W. Jones ; Rachel聽M. McLoughlin ; Louise McLeod ; Victoria聽J. Hammond ; Javier Uceda ; Anwen聽S. Williams ; Mark Lambie ; Thomas聽L. Foster ; Chia-Te Liao ; Christopher聽M. Rice ; Claire聽J. Greenhill ; Chantal聽S. Colmont ; Emily Hams ; Barbara Coles ; Ann Kift-Morgan ; Zarabeth Newton ; Katherine聽J. Craig ; John聽D. Williams ; Geraint聽T. Williams ; Simon聽J. Davies ; et al.
• 刊名：Immunity
• 出版年：16 January, 2014
• 年：2014
• 卷：40
• 期：1
• 页码：40-50
• 全文大小：1753 K

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Summary

Fibrosis in response to tissue damage or persistent inflammation is a pathological hallmark of many chronic degenerative diseases. By using a model of acute peritoneal inflammation, we have examined how repeated inflammatory activation promotes fibrotic tissue injury. In this context, fibrosis was strictly dependent on interleukin-6 (IL-6). Repeat inflammation induced IL-6-mediated T helper 1 (Th1) cell effector commitment and the emergence of STAT1 (signal transducer and activator of transcription-1) activity within the peritoneal membrane. Fibrosis was not observed in mice lacking interferon-纬 (IFN-纬), STAT1, or RAG-1. Here, IFN-纬 and STAT1 signaling disrupted the turnover of extracellular matrix by metalloproteases. Whereas IL-6-deficient mice resisted fibrosis, transfer of polarized Th1 cells or inhibition of MMP activity reversed this outcome. Thus, IL-6 causes compromised tissue repair by shifting acute inflammation into a more chronic profibrotic state through induction of Th1 cell responses as a consequence of recurrent inflammation.