期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 397, 期 2, 页码 311-317出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.05.109
关键词
Phosphoinositide 3-kinase-gamma; Inflammation; Pulmonary fibrosis; Bleomycin; AS605240
资金
- National 863 Project of China [2007AA021201]
- National Project of China [2009Z-X09501-015]
Phosphoinositide 3-kinase-gamma (PI3K gamma) has been identified to play the critical roles in inflammatory cells activation and recruitment in multiply inflammatory diseases and it promised to be a prospective target for relevant inflammatory diseases therapy. AS605240, a selective PI3K gamma inhibitor, has been proved effective on several inflammatory diseases. In this study, we investigated the protective effect of AS605240 on bleomycin-induced pulmonary fibrosis in rats. Our results showed that orally administration of AS605240 significantly prevented lung inflammation and reduced collagen deposition. AS605240 also inhibited augmented expression of TNF-alpha and IL-1 beta induced by bleomycin instillation. Moreover, the mRNA levels of TNF-alpha and IL-1 beta in lung were remarkably suppressed. Histological assessment found that AS605240 reduced the expression of TGF-beta(1) and prevented T lymphocytes infiltration to lung. Phospho-Akt level in inflammatory cells by blocking PI3K gamma was down-regulated and the inhibition of Akt phosphorylation was further confirmed by Western blot. Our findings illustrated that AS605240 was effective for preventing pulmonary fibrosis by suppressing inflammatory cells recruitment and production of inflammatory cytokines. These findings also suggest that PI3K gamma may be a useful target in treating inflammation diseases and AS605240 may represent a promising novel agent for the future therapy of pulmonary fibrosis. (C) 2010 Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据