Interleukin-1β (IL-1β) has been recognized as a potent stimulus for the synthesis of prostaglandin (PG), which has been implicated in inflammatory responses of the airways. However, the mechanisms underlying IL-1β-induced cyclooxygenase (COX) expression and PGE2 synthesis via activation of p42/p44 and p38 mitogen-activated protein kinases (MAPKs) in human tracheal smooth muscle cells (HTSMCs) are not completely understood. We found that IL-1β increased COX-2 expression and PGE2 synthesis in time- and concentration-dependent manners. Both specific phosphatidylcholine-phospholipase C inhibitor (D609) and protein kinase C inhibitor (GF109203X) attenuated IL-1β-induced responses in HTSMCs. IL-1β-induced COX-2 expression and PGE2 synthesis were also inhibited by an inhibitor of MEK1/2 (PD98059) and inhibitors of p38 MAPK (SB203580 and SB202190), respectively, suggesting the involvement of p42/p44 and p38 MAPKs in these responses. This hypothesis was further supported by the transient activation of p42/p44 and p38 MAPKs induced by IL-1β. Furthermore, IL-1β-induced activation of nuclear factor-ĸB (NF-ĸB) was inversely correlated with the degradation of IĸB-α in HTSMCs. IL-1β-induced COX-2 expression and PGE2 synthesis were inhibited by the NF-ĸB inhibitor pyrrolidinedithiocarbamate. These findings suggest that the expression of COX-2 is correlated with the release of PGE2 from IL-1β-challenged HTSMCs, which is mediated, at least in part, through p42/p44 and p38 MAPKs and NF-ĸB signaling pathways in HTSMCs.

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