Takahashi S, Shigeta J, Inoue H, Tanabe T, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Am J Physiol. 1998 Nov;275(5):G1137-45. doi: 10.1152/ajpgi.1998.275.5.G1137.
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-beta1 (TGF-beta1) 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-beta1 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-beta1.
据报道，环氧化酶-2（COX-2）可能在胃溃疡愈合中起关键作用。我们研究了COX-2在大鼠醋酸溃疡中的定位以及COX-2 mRNA表达的调控。溃疡组织中PGE2的产生增加，但完整组织中未增加。COX-2 mRNA表达仅在溃疡组织中被诱导，并且在成纤维细胞、单核细胞/巨噬细胞和粒细胞中发现了COX-2蛋白。一种选择性COX-2抑制剂可抑制溃疡组织中PGE2产生的增加。白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和转化生长因子-β1（TGF-β1）的mRNA也仅在溃疡组织中表达。在分离的溃疡底部培养物中，阻断IL-1β和TNF-α可降低COX-2 mRNA表达和PGE2产生。相反，通过阻止TGF-β1的作用可促进COX-2 mRNA表达和PGE2产生。这些结果表明，COX-2蛋白高度定位于大鼠胃溃疡底部，并且COX-2 mRNA表达可能受到IL-1β和TNF-α的正向调节以及TGF-β1的负向调节。
