title: Induction of cyclooxygenase-2 expression in human tracheal smooth muscle cells by interleukin-1beta: involvement of p42/p44 and p38 mitogen-activated protein kinases and nuclear factor-kappaB.
abstract: Interleukin-1beta (IL-1beta) 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-1beta-induced cyclooxygenase (COX) expression and PGE(2) 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-1beta increased COX-2 expression and PGE(2) synthesis in time- and concentration-dependent manners. Both specific phosphatidylcholine-phospholipase C inhibitor (D609) and protein kinase C inhibitor (GF109203X) attenuated IL-1beta-induced responses in HTSMCs. IL-1beta-induced COX-2 expression and PGE(2) 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-1beta. Furthermore, IL-1beta-induced activation of nuclear factor-kappaB (NF-kappaB) was inversely correlated with the degradation of IkappaB-alpha in HTSMCs. IL-1beta-induced COX-2 expression and PGE(2) synthesis were inhibited by the NF-kappaB inhibitor pyrrolidinedithiocarbamate. These findings suggest that the expression of COX-2 is correlated with the release of PGE(2) from IL-1beta-challenged HTSMCs, which is mediated, at least in part, through p42/p44 and p38 MAPKs and NF-kappaB signaling pathways in HTSMCs.
authors.affiliation: Department of Anesthetics, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Lin
authors.forename: Chi-Chin
authors.initials: CC
authors.lastname: Sun
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Luo
authors.forename: An-Chi
authors.initials: AC
authors.lastname: Tsai
authors.forename: Chin-Sung
authors.initials: CS
authors.lastname: Chien
authors.forename: Li-Der
authors.initials: LD
authors.lastname: Hsiao
authors.forename: Chiang-Wen
authors.initials: CW
authors.lastname: Lee
authors.forename: Jen-Tsung
authors.initials: JT
authors.lastname: Hsieh
authors.forename: Chuen-Mao
authors.initials: CM
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D017931:DNA Primers; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D016328:NF-kappa B / Q000502:physiology*; D009636:Norbornanes; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D001952:Bridged-Ring Compounds; D017931:DNA Primers; D004791:Enzyme Inhibitors; D004963:Estrenes; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D009636:Norbornanes; D011760:Pyrrolidinones; D013859:Thiocarbamates; D013871:Thiones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C046498:tricyclodecane-9-yl-xanthogenate; D019833:Genistein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D002118:Calcium