title: Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats.
abstract: Clinical and experimental findings had indicated that cigarette smoke exposure, and cyclooxygenase-2, are strongly associated with inflammatory bowel disease. The present study aimed to evaluate the role of cyclooxygenase-2 in the pathogenesis of experimental inflammatory bowel disease as well as in the adverse action of cigarette-smoke exposure. Rats were pretreated with different cyclooxygenase-2 inhibitors (indomethacin, nimesulide, or SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide)) along with cigarette-smoke exposure before 2,4,6-trinitrobenzenesulfonic acid-enema. Results indicated that pretreatment with cyclooxygenase-2 inhibitors not only protected against 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also attenuated the potentiating effect of cigarette-smoke exposure on colonic damage. Furthermore, the colonic cyclooxygenase-2 protein and mRNA expression was markedly induced by 2,4,6-trinitrobenzenesulfonic acid-enema, and it was potentiated further by cigarette-smoke exposure, while the cyclooxygenase-1 expression was not changed. The present study suggests that the highly induced cyclooxygenase-2 expression not only plays a pathogenic role in 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also contributes to the adverse action of cigarette-smoke exposure on this disorder.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 1/F, Li Shu Fan Bldg., 5 Sassoon Road, SAR, Hong Kong, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.forename: E S
authors.initials: ES
authors.lastname: Liu
authors.forename: J K
authors.initials: JK
authors.lastname: Ko
authors.forename: B C
authors.initials: BC
authors.lastname: Wong
authors.forename: Y
authors.initials: Y
authors.lastname: Ye
authors.forename: S
authors.initials: S
authors.lastname: Lam
authors.forename: C
authors.initials: C
authors.lastname: Cho
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003092:Colitis / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000201:enzymology / Q000517:prevention & control; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D013449:Sulfonamides; D014028:Tobacco Smoke Pollution; D007975:Leukotriene B4; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; C012655:nimesulide; D007213:Indomethacin