Interleukin-1β-induced cyclooxygenase-2 expression is mediated through activation of p42/44 and p38 MAPKS, and NF-κB pathways in canine tracheal smooth muscle cells

摘要: Interleukin-beta (IL-1beta) was found to induce inflammatory responses in the airways, which exerted a potent stimulus for PG synthesis. This study determine mechanisms of IL-1beta-enhanced cyclooxygenase (COX)-2 expression associated with PGE(2) synthesis tracheal smooth muscle cells (TSMCs). IL-1beta markedly increased COX-2 and formation time- concentration-dependent manner TSMCs. Both response were attenuated by tyrosine kinase inhibitor, genistein, phosphatidylcholine-phospholipase C D609, phosphatidylinositol-phospholipase U73122, protein inhibitors, GF109203X staurosporine, removal Ca(2+) addition BAPTA/AM plus EGTA, phosphatidylinositol 3-kinase (PI3-K) LY294002 wortmannin. IL-1beta-induced activation NF-kappaB correlated degradation IkappaB-alpha activation, expression, inhibited dominant negative mutants NIK IKK-alpha, but not IKK-beta. completely PD98059 (an inhibitor MEK1/2) SB203580 p38 inhibitor), these two inhibitors had no effect on indicating that p42/44 MAPK signalling pathways independently required responses. These findings suggest correlates release from IL-1beta-challenged TSMCs, at least part, mediated through MAPKs canine IL-1beta-mediated modulated PLC, Ca(2+), PKC, kinase, PI3-K cells.