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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Colitis / enzymology
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Colitis / etiology
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Colitis / prevention & control*
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Colon / drug effects
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Colon / metabolism
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Colon / pathology
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology*
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Gene Expression Regulation, Enzymologic / drug effects
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Indomethacin / pharmacology
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Inflammation / enzymology
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Inflammation / prevention & control
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Inflammatory Bowel Diseases / chemically induced
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Inflammatory Bowel Diseases / enzymology
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Inflammatory Bowel Diseases / prevention & control
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Leukotriene B4 / metabolism
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Male
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Membrane Proteins
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Peroxidase / drug effects
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Peroxidase / metabolism
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism
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Prostaglandins / biosynthesis
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Reverse Transcriptase Polymerase Chain Reaction
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Sulfonamides / pharmacology
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Tobacco Smoke Pollution / adverse effects*
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Trinitrobenzenesulfonic Acid / administration & dosage
Substances
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Membrane Proteins
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Prostaglandins
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RNA, Messenger
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Sulfonamides
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Tobacco Smoke Pollution
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Leukotriene B4
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Trinitrobenzenesulfonic Acid
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Peroxidase
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Cyclooxygenase 1
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Ptgs1 protein, rat
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nimesulide
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Indomethacin