| First Author | Fielding CA | Year | 2014 |
| Journal | Immunity | Volume | 40 |
| Issue | 1 | Pages | 40-50 |
| PubMed ID | 24412616 | Mgi Jnum | J:209391 |
| Mgi Id | MGI:5567050 | Doi | 10.1016/j.immuni.2013.10.022 |
| Citation | Fielding CA, et al. (2014) Interleukin-6 signaling drives fibrosis in unresolved inflammation. Immunity 40(1):40-50 |
| abstractText | 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-gamma (IFN-gamma), STAT1, or RAG-1. Here, IFN-gamma 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. |
