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Am J Physiol Gastrointest Liver Physiol 275: G1137-G1145, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 5, G1137-G1145, November 1998

Localization of cyclooxygenase-2 and regulation of its mRNA expression in gastric ulcers in rats

Satoru Takahashi1, Jun-Ichi Shigeta1, Hiroyasu Inoue2, Tadashi Tanabe2, and Susumu Okabe1

1 Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414; and 2 Department of Pharmacology, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan

It has been reported that cyclooxygenase-2 (COX-2) may play a crucial role in gastric ulcer healing. We examined the localization of COX-2 and the regulation of COX-2 mRNA expression in acetic acid ulcers in rats. PGE2 production was elevated in ulcerated tissue but not in intact tissue. COX-2 mRNA expression was induced in only the ulcerated tissue, and COX-2 protein was found in fibroblasts, monocytes/macrophages, and granulocytes. A selective COX-2 inhibitor inhibited increased PGE2 production by the ulcerated tissue. Interleukin-1beta (IL-1beta ), tumor necrosis factor-alpha (TNF-alpha ), and transforming growth factor-beta 1 (TGF-beta 1) mRNAs were also expressed only in the ulcerated tissue. In a culture of isolated ulcer base, blockade of IL-1beta and TNF-alpha reduced COX-2 mRNA expression and PGE2 production. In contrast, COX-2 mRNA expression and PGE2 production were promoted by prevention of TGF-beta 1 action. These results indicate that COX-2 protein is highly localized in the base of gastric ulcers in rats and that COX-2 mRNA expression might be regulated positively by IL-1beta and TNF-alpha and negatively by TGF-beta 1.

prostaglandin; interleukin-1beta ; tumor necrosis factor-alpha ; transforming growth factor-beta 1


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