Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice

BACKGROUND & AIMS: The role of two forms of cyclooxygenase (COX-1 and COX-2) in gastric mucosal lesions is not well understood. The regulation of both forms of COX and the effect of COX-2 on the repair process of gastric mucosal lesions in mice were investigated. METHODS: Gastric mucosal erosions and ulcers were induced experimentally in mice. The level of COX messenger RNA (mRNA) was determined by reverse- transcription polymerase chain reaction. COX proteins were detected by Western blot analysis, and COX activity was determined in the presence or absence of NS-398, a specific COX-2 antagonist. The effects of long- term administration of NS-398 on gastric ulcers were examined. RESULTS: COX-2 mRNA levels were not detected in control conditions but were high during the acute stages of gastric erosions and ulcers. COX-2 protein was detected 5 days after ulcer induction but not in control mice. Gastric ulceration was not associated with a change in COX-1 mRNA and protein levels. Administration of NS-398 to mice with ulcers at acute stages impaired the healing of ulcers. CONCLUSIONS: High levels of COX- 2 mRNA and protein during the acute stages of gastric mucosal lesions may be involved in the repair process of these lesions in mice. (Gastroenterology 1997 Feb;112(2):387-97)