TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation.
TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation.
复制标题
TNF 受体相关因子 5 控制制瘤素 M 介导的肺部炎症。
DOI：
10.1016/j.bbrc.2018.03.186
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Ishii N.
中科院分区：
文献类型：
--
作者：
Machiyama T;So T;Okuyama Y;Kobayashi S;Phung HT;Asao A;Harigae H;Ishii N.
抑瘤素M（Oncostatin M，OSM）参与多种人类炎症性疾病的发病机制，包括肺部炎症和纤维化。虽然越来越多的证据表明OSM介导了肺部炎症，但OSM对肺部炎症的确切机制仍不清楚。在本研究中，我们发现OSM受体在小鼠肺的内皮细胞和基质/成纤维细胞上大量表达，在体外，OSM刺激上调了新鲜分离的野生型小鼠肺基质/成纤维细胞上的血管细胞粘附分子-1（VCAM-1），从而促进了肺组织中嗜酸性粒细胞的浸润。然而，来自TNF受体相关因子5（TRAF 5）缺陷小鼠的这些细胞在OSM刺激后未能显示VCAM-1表达的增加。此外，与野生型小鼠相比，Traf 5 −/−小鼠在鼻内给予OSM后，在嗜酸性粒细胞浸润方面表现出显著减弱的肺部炎症。这些结果表明TRAF 5可能通过诱导肺基质/成纤维细胞活化而关键地参与OSM介导的肺部炎症。
Oncostatin M (OSM) is involved in pathogenesis of several human inflammatory diseases including lung inflammation and fibrosis. Although accumulating evidence indicates that OSM mediates lung inflammation, the precise mechanism for OSM on lung inflammation still remains unclear. In this study, we found that OSM receptor was abundantly expressed on endothelial and stromal/fibroblast cells in the lung of mice.In vitrostimulation with OSM upregulated vascular cell adhesion molecule-1 (VCAM-1), which promotes eosinophil infiltration in the lung tissues, on freshly-isolated lung stromal/fibroblast cells from wild-type mice. However, these cells from TNF receptor associated factor 5 (TRAF5)-deficient mice failed to show the increase in VCAM-1 expression after OSM stimulation. Furthermore,Traf5−/−mice showed markedly attenuated lung inflammation in terms of eosinophil infiltration upon intranasal administration with OSM as compared to wild-type mice. These results indicate that TRAF5 is crucially involved in OSM-mediated lung inflammation probably by inducing lung stromal/fibroblast cell activation.