Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats.
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.
Guo
X
X
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.
Liu
E S
ES
Ko
J K
JK
Wong
B C
BC
Ye
Y
Y
Lam
S
S
Cho
C
C
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
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