IL-1β activates p44/42 and p38 mitogen-activated protein kinases via different pathways in cat esophageal smooth muscle cells

摘要

AIM:To examine the pathway related to the IL-1β-induced activation of mitogen-activated protein(MAP)kinases in cat esophageal smooth muscle cells.METHODS:Culture of the esophageal smooth musclecells from cat was prepared.Specific inhibitors weretreated before applying the IL-1β.Western blot analysiswas performed to detect the expressions of COX,iNOSand MAP kinases.RESULTS:In the primary cultured cells,although IL-1βfailed to upregulate the COX and iNOS levels,the levelsof the phosphorylated forms of p44/42 MAP kinase andp38 MAP kinase increased in both concentration-andtime-dependent manner,of which the level of activationreached a maximum within 3 and 18 h,respectively.The pertussis toxin reduced the level of p44/42 MAPkinase phosphorylation.Tyrphostin 51 and genistein alsoinhibited this activation.Neomycin decreased the densityof the p44/42 MAP kinase band to the basal level.Phosphokinase C(PKC)was found to play a mediatingrole in the IL-1β-induced p44/42 MAP kinase activity.In contrast,the activation of p38 MAP kinase wasinhibited only by a pretreatment with forskolin,and wasunaffected by the other compounds.CONCLUSION:Based on these results,IL-1β-inducedp44/42 MAP kinase activation is mediated by the Giprotein,tyrosine kinase,phospholipase C(PLC)andPKC.The pathway for p38 MAP kinase phosphorylationis different from that of p44/42 MAP kinase,suggestingthat it piays a different role in the cellular response to IL-1β.