Protective role of reactive oxygen species in endotoxin-induced lung inflammation through modulation of IL-10 expression.
Protective role of reactive oxygen species in endotoxin-induced lung inflammation through modulation of IL-10 expression.
复制标题
DOI：
10.4049/jimmunol.1101323
复制
发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Christman JW
中科院分区：
文献类型：
--
作者：
Deng J;Wang X;Qian F;Vogel S;Xiao L;Ranjan R;Park H;Karpurapu M;Ye RD;Park GY;Christman JW
由NADPH氧化酶产生的活性氧物种(ROS)通常被认为是促炎的，而ROS在调节炎症反应的消退中起着关键作用，这似乎是违反直觉的。然而，我们观察到，在内毒素诱导的非感染性脓毒症的整个动物模型中，巨噬细胞中NADPH氧化酶的p47Phox成分的缺失与炎症的矛盾加剧有关。我们通过询问采用互补方法学的四个单独的体内模型证实了这一观察结果，这些模型包括使用p47Phox−/−小鼠、p47Phox−/−骨髓嵌合体小鼠、过继转移p47Phox−/−小鼠的巨噬细胞以及隔离的灌流性肺水肿模型，这些模型都表明巨噬细胞中过度的急性炎症和p47Phox缺乏之间存在关系。机制数据表明，细胞和小鼠体内的ROS缺乏导致内毒素治疗后IL-10的产生减少，至少部分是通过减弱Akt-GSK3-β信号通路，而重组IL-10可以逆转这一现象。我们的数据支持这一创新概念，即ROS的产生对于急性肺炎症的反调节是必不可少的。
Reactive Oxygen Species (ROS) generated by NADPH oxidase are generally known to be pro-inflammatory, and it seems to be counterintuitive that ROS play a critical role in regulating the resolution of the inflammatory response. However, we observed that deficiency of the p47phox component of NADPH oxidase in macrophages was associated with a paradoxical accentuation of inflammation in a whole animal model of non-infectious sepsis induced by endotoxin. We have confirmed this observation by interrogating four separate in vivo models that employ complementary methodology including the use of p47phox−/− mice, p47phox−/− bone marrow chimera mice, adoptive transfer of macrophages from p47phox−/− mice, and an isolated perfused lung edema model that all point to a relationship between excessive acute inflammation and p47phox deficiency in macrophages. Mechanistic data indicate that ROS deficiency in both cells and mice results in decreased production of IL-10 in response to treatment with LPS, at least in part, through attenuation of the Akt-GSK3-β signal pathway and that it can be reversed by the administration of recombinant IL-10. Our data support the innovative concept that generation of ROS is essential for counter-regulation of acute lung inflammation.
登录
查看更多内容
影响因子：
3.1
作者：
Deckert, M;Soltek, S;Schlüter, D
通讯作者：
Schlüter, D
DOI：
10.1164/ajrccm.162.3.9906129
发表时间：
2000-09-01
影响因子：
24.7
作者：
Blackwell, TS;Yull, FE;Kerr, LD
通讯作者：
Kerr, LD
DOI：
10.1084/jem.20102049
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bulua AC;Simon A;Maddipati R;Pelletier M;Park H;Kim KY;Sack MN;Kastner DL;Siegel RM
通讯作者：
Siegel RM
影响因子：
5.5
作者：
Everhart, MB;Han, W;Blackwell, TS
通讯作者：
Blackwell, TS
DOI：
10.1165/ajrcmb.26.5.4748
发表时间：
2002-05-01
影响因子：
6.4
作者：
Koay, MA;Gao, X;Christman, JW
通讯作者：
Christman, JW