Interleukin-6 signaling drives fibrosis in unresolved inflammation

Ceri A. Fielding, Gareth W. Jones, Rachel M. McLoughlin, Louise McLeod, Victoria J. Hammond, Javier Uceda, Anwen S. Williams, Mark Lambie, Thomas L. Foster, Chia Te Liao, Christopher M. Rice, Claire J. Greenhill, Chantal S. Colmont, Emily Hams, Barbara Coles, Ann Kift-Morgan, Zarabeth Newton, Katherine J. Craig, John D. Williams, Geraint T. WilliamsSimon J. Davies, Ian R. Humphreys, Valerie B. O'Donnell, Philip R. Taylor, Brendan J. Jenkins, Nicholas Topley, Simon A. Jones

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196 引文 斯高帕斯(Scopus)

摘要

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-γ (IFN-γ), STAT1, or RAG-1. Here, IFN-γ 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.

原文英語
頁(從 - 到)40-50
頁數11
期刊Immunity
40
發行號1
DOIs
出版狀態已發佈 - 一月 16 2014
對外發佈

ASJC Scopus subject areas

  • 免疫學和過敏
  • 免疫學
  • 傳染性疾病

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