Interleukin-6 signaling drives fibrosis in unresolved inflammation.
Interleukin-6 signaling drives fibrosis in unresolved inflammation.
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DOI：
10.1016/j.immuni.2013.10.022
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发表时间：
2014-01-16
期刊：
影响因子：
32.4
通讯作者：
Jones, Simon A.
中科院分区：
文献类型：
--
作者：
Fielding, Ceri A.;Jones, Gareth W.;McLoughlin, Rachel M.;McLeod, Louise;Hammond, Victoria J.;Uceda, Javier;Williams, Anwen S.;Lambie, Mark;Foster, Thomas L.;Liao, Chia-Te;Rice, Christopher M.;Greenhill, Claire J.;Colmont, Chantal S.;Hams, Emily;Coles, Barbara;Kift-Morgan, Ann;Newton, Zarabeth;Craig, Katherine J.;Williams, John D.;Williams, Geraint T.;Davies, Simon J.;Humphreys, Ian R.;O'Donnell, Valerie B.;Taylor, Philip R.;Jenkins, Brendan J.;Topley, Nicholas;Jones, Simon A.
对组织损伤或持续性炎症作出反应的纤维化是许多慢性退行性疾病的病理特征。通过使用急性腹膜炎症模型，我们研究了反复炎症激活如何促进纤维组织损伤。在这种情况下，纤维化严格依赖于白细胞介素6(IL-6)。反复炎症可诱导IL-6介导的辅助性T细胞1(Th1)细胞效应分子的表达，并在腹膜内出现STAT1(信号转导和转录激活因子-1)活性。在缺乏干扰素-γ(干扰素-γ)、STAT1或RAG-1的小鼠中没有观察到纤维化。在此，干扰素-γ和STAT1信号通过金属蛋白酶干扰细胞外基质的周转。尽管IL-6缺乏的小鼠抵抗纤维化，但极化的Th1细胞的转移或对基质金属蛋白酶活性的抑制逆转了这一结果。因此，由于反复发炎，IL-6通过诱导Th1细胞反应，将急性炎症转化为更慢性的纤维化状态，从而导致受损的组织修复。反复急性消退炎症导致过度组织损伤IL-6调节促纤维化干扰素-γ分泌的T细胞干扰素-γ增加间质组织中有害的STAT1信号转导STAT1活性改变细胞外基质的动态平衡控制促进纤维化
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. Repeated acute resolving inflammation leads to excessive tissue damage IL-6 regulates profibrotic IFN-γ-secreting T cells IFN-γ increases detrimental STAT1 signaling in stromal tissue STAT1 activity alters homeostatic control of extracellular matrix to promote fibrosis
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DOI：
10.1084/jem.20030077
发表时间：
2003-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kano A;Wolfgang MJ;Gao Q;Jacoby J;Chai GX;Hansen W;Iwamoto Y;Pober JS;Flavell RA;Fu XY
通讯作者：
Fu XY
影响因子：
4.4
作者：
Ho, Hao H.;Antoniv, Taras T.;Ji, Jong-Dae;Ivashkiv, Lionel B.
通讯作者：
Ivashkiv, Lionel B.
影响因子：
29.4
作者：
Judd, Louise M.;Bredin, Karin;Giraud, Andrew S.
通讯作者：
Giraud, Andrew S.
影响因子：
4.4
作者：
Jones, Gareth W.;McLoughlin, Rachel M.;Jones, Simon A.
通讯作者：
Jones, Simon A.
影响因子：
64.8
作者：
HIRANO, T;YASUKAWA, K;KISHIMOTO, T
通讯作者：
KISHIMOTO, T