Interleukin-6 Signaling Drives Fibrosis in Unresolved Inflammation

被引：355

作者：

Fielding, Ceri A. ^{[1
]}

Jones, Gareth W. ^{[1
]}

McLoughlin, Rachel M. ^{[1
]}

McLeod, Louise ^{[2
]}

Hammond, Victoria J. ^{[1
]}

Uceda, Javier ^{[1
]}

Williams, Anwen S. ^{[1
]}

Lambie, Mark ^{[3
,4
]}

Foster, Thomas L. ^{[1
]}

Liao, Chia-Te ^{[1
]}

Rice, Christopher M. ^{[1
]}

Greenhill, Claire J. ^{[1
]}

Colmont, Chantal S. ^{[1
]}

Hams, Emily ^{[1
]}

Coles, Barbara ^{[1
]}

Kift-Morgan, Ann ^{[1
]}

Newton, Zarabeth ^{[1
]}

Craig, Katherine J. ^{[5
]}

Williams, John D. ^{[5
]}

Williams, Geraint T. ^{[6
]}

Davies, Simon J. ^{[3
,4
]}

Humphreys, Ian R. ^{[1
]}

O'Donnell, Valerie B. ^{[1
]}

Taylor, Philip R. ^{[1
]}

Jenkins, Brendan J. ^{[2
]}

Topley, Nicholas ^{[1
]}

Jones, Simon A. ^{[1
]}

机构：

[1] Cardiff Univ, Sch Med, Cardiff Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales

[2] Monash Univ, Monash Inst Med Res, Ctr Innate Immun & Infect Dis, Clayton, Vic 3168, Australia

[3] Keele Univ, Univ Hosp North Staffordshire, Dept Nephrol, Stoke On Trent ST4 7QB, Staffs, England

[4] Keele Univ, Inst Sci & Technol Med, Stoke On Trent ST4 7QB, Staffs, England

[5] Cardiff Univ, Sch Med, Inst Mol & Expt Med, Inst Nephrol, Cardiff CF14 4XN, S Glam, Wales

[6] Cardiff Univ, Sch Med, Inst Canc & Genet, Sect Pathol, Cardiff CF14 4XN, S Glam, Wales

来源：

IMMUNITY | 2014年 / 40卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

REGULATORY T-CELLS; HYPER-IGE SYNDROME; IFN-GAMMA; NEUTROPHIL TRAFFICKING; RESPIRATORY-INFECTION; MOLECULAR-MECHANISMS; PERITONEAL-DIALYSIS; STAT3; ACTIVATION; INTERFERON-GAMMA; DENDRITIC CELLS;

D O I：

10.1016/j.immuni.2013.10.022

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

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-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 pro-fibrotic state through induction of Th1 cell responses as a consequence of recurrent inflammation.

引用

页码：40 / 50

页数：11

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