MAPK pathway mediates EGR-1-HSP70-dependent cigarette smoke-induced chemokine production

被引:69
作者
Li, Chao-Jun
Ning, Wen
Matthay, Michael A.
Feghali-Bostwick, Carol A.
Choi, Augustine M. K.
机构
[1] Univ Pittsburgh, Sch Med, Dept Med, Pulm Allergy & Crit Care Med Div, Pittsburgh, PA 15213 USA
[2] Nanjing Normal Univ, Life Sci Coll, Jiangsu Key Lab Mol Med Biotechnol, Nanjing, Peoples R China
[3] Nanjing Univ, Model Anim Res Ctr, Nanjing 210008, Peoples R China
[4] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA
关键词
chronic obstructive pulmonary disease; cigarette smoke extract; early growth response-1; interleukin-8; 70-kDa heat shock protein;
D O I
10.1152/ajplung.00194.2006
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Cigarette smoking, a major risk factor for chronic obstructive pulmonary disease, can cause airway inflammation, airway narrowing, and loss of elasticity, leading to chronic airflow limitation. In this report, we sought to define the signaling pathways activated by smoke and to identify molecules responsible for cigarette smoke-induced inflammation. We applied cigarette smoke water extract (CSE) to primary human lung fibroblasts and found that CSE significantly increased CXC chemokine IL-8 production. Meanwhile, 70-kDa heat shock protein (HSP70) was also induced by CSE in a dose-and time-dependent manner. CSE treatment stimulated HSP70 secretion by primary fibroblasts, which augmented IL-8 production. This was further confirmed by exogenously added recombinant HSP70. Using HSP70 small interfering RNA, we confirmed that CSE-induced chemokine production was dependent on heat shock protein expression. Further investigation showed that CSE could also stimulate early growth response-1 (EGR-1) in an ERK-dependent manner and that the expression of HSP70 was EGR-1 dependent. In view of these findings, we hypothesize that the MAPK-EGR-1-HSP70 pathway regulates the cigarette smoke-induced inflammatory process.
引用
收藏
页码:L1297 / L1303
页数:7
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