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
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.