EXACERBATION OF INFLAMMATION-ASSOCIATED COLONIC INJURY IN RAT THROUGHINHIBITION OF CYCLOOXYGENASE-2

Citation
Bk. Reuter et al., EXACERBATION OF INFLAMMATION-ASSOCIATED COLONIC INJURY IN RAT THROUGHINHIBITION OF CYCLOOXYGENASE-2, The Journal of clinical investigation, 98(9), 1996, pp. 2076-2085
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
98
Issue
9
Year of publication
1996
Pages
2076 - 2085
Database
ISI
SICI code
0021-9738(1996)98:9<2076:EOICII>2.0.ZU;2-J
Abstract
Cyclooxygenase type 1 is constitutively expressed and accounts for syn thesis of prostaglandins in the normal gastrointestinal tract, Cycloox ygenase-2 is expressed at sites of inflammation. Selective inhibitors of cyclooxygenase-2 have been suggested to spare gastrointestinal pros taglandin synthesis, and therefore lack the ulcerogenic effects associ ated with standard nonsteroidal antiinflammatory drugs. However, the e ffects of cyclooxygenase-2 inhibitors on inflamed gastrointestinal muc osa have not been examined, We examined cyclooxygenase-2 mRNA and prot ein expression before and after induction of colitis in the rat, the c ontribution of cyclooxygenase-2 to colonic prostaglandin synthesis dur ing colitis and the effects of selective inhibitors of cyclooxygenase- 2 on colonic injury in this model. Cyclooxygenase-2 mRNA expression in creased three to sixfold during the period 24 h to 1 wk after inductio n of colitis, with marked increases in cyclooxygenase-2 protein expres sion in the lamina propria and muscularis of the colon during colitis, Cyclooxygenase-1 expression (mRNA and protein) was not affected by th e induction of colitis. The prostaglandins produced during colitis wer e largely derived from cyclooxygenase-2, Treatment with selective cycl ooxygenase-2 inhibitors resulted in exacerbation of colitis, with perf oration occurring when the compounds were administered for a week. The se studies demonstrate that suppression of cyclooxygenase-2 can result in exacerbation of inflammation-associated colonic injury.