Thrombin induces cyclooxygenase-2 expression via the ERK and NF-kB pathways in human lung fibroblasts

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題名:	Thrombin induces cyclooxygenase-2 expression via the ERK and NF-kB pathways in human lung fibroblasts
作者:	陳炳常;施崇鴻 Shih CH;Bien MY;Chiang LL;Su CL;Lin CH;Chen BC
貢獻者:	呼吸治療學系
日期:	2009
上傳時間:	2009-08-24 11:32:43 (UTC+8)
摘要:	There is growing evidence that increased expression of cyclooxygenase-2 (COX-2) in the lungs of patients is a key event in the pathogenesis of lung diseases. In this study, we investigated the involvement of the extracellular signal-regulated kinase (ERK), IκB kinase α/β (IKKα/β), and nuclear factor-κB (NF-κB) signaling pathways in thrombin-induced COX-2 expression in human lung fibroblasts (WI-38). Treatment of WI-38 cellswith thrombin caused increased COX-2 expression in a concentration- and time-dependent manner. Treatment of WI-38 cells with PD 98059 (2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one, a MEK inhibitor) inhibited thrombininduced COX-2 expression and COX-2-luciferase activity. Stimulation of cells with thrombin caused an increase in ERK phosphorylation in a time-dependentmanner. In addition, treatment of WI-38 cells with Bay 117082, an IκB phosphorylation inhibitor, and pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, inhibited thrombininduced COX-2 expression. The thrombin-induced increase in COX-2-luciferase activity was also blocked by the dominant negative IκBα mutant (IκBαM). Treatment of WI-38 cells with thrombin induced IKKα/β and IκBα phosphorylation, IκBα degradation, and κB-luciferase activity. The thrombin-mediated increases in IKKα/β phosphorylation and κB-luciferase activitywere inhibited by PD98059. Taken together, these results suggest that the ERK-dependent IKKα/β/NF-κB signaling pathway plays an important role in thrombin-induced COX-2 expression in human lung fibroblasts.
關聯:	European Journal of Pharmacology.
資料類型:	article
顯示於類別:	[呼吸治療學系] 期刊論文

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