- 作者: Chie-Chung Lin; Chi-Chin Sun; Shu-Fen Luo; An-Chi Tsai; Chin-Sung Chien; Li-Der Hsiao; Chiang-Wen Lee; Jen-Tsung Hsieh; Chuen-Mao Yang
- 作者服務機構: Departments of Anesthetics and Ophthalmology, Chang Gung Memorial Hospital, Department of Internal Medicine and Ppysiology and Pharmacology, Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan,ROC
- 中文摘要: --
- 英文摘要: Interleukin-1β (IL-1β)has been recognized as a potentstimulus for the synthesis of prostaglandin (PG), whichhas been implicated in inflammatory responses of theairways. However, the mechanisms underlying IL-1β-induced cyclooxygenase (COX) expression and PGE2synthesis via activation of p42/p44 and p38 mitogen-acti-vated protein kinases (MAPKs) in human trachealsmooth muscle cells (HTSMCs)are not completely un-derstood. We found that IL-1β increased COX-2 expres-sion and PGE synthesis in time- and concentration-dependent manners. Both specific phosphatidylcholine-phospholipase C inhibitor (D609) and protein kinase Cinhibitor (GF109203X) attenuated IL-1β-induced re-sponses in HTSMCs. IL-1β-induced COX-2 expressionand PGE synthesis were also inhibited by an inhibi-tor of MEK1/2 (PD98059) and inhibitors of p38 MAPK(SB203580 and SB202190), respectively, suggesting theinvolvement of p42/p44 and p38 MAPKs in these re-sponses. This hypothesis was further supported by thetransient activation of p42/p44 and p38 MAPKs inducedby IL-1β. Furthermore, IL-1β-induced activation of nu-clear factor-κB (NF-κB) was inversely correlated with thedegradation of IKB-α in HTSMCs. IL-1β-induced COX-2expression and PGE synthesis were inhibited by the NF-κB inhibitor pyrrolidinedithiocarbamate. These findingssuggest that the expression of COX-2 is correlated withthe release of PGE from IL-1β-challenged HTSMCs,which is mediated; at least in part, through p42/p44 andp38 MAPKs and NF-κB signaling pathways in HTSMCs.
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