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  • Title: Irritant-induced cyclooxygenase-2 is involved in the defense mechanism of the gastric mucosa in mice.
    Author: Miyake K, Tsukui T, Wada K, Tatsuguchi A, Futagami S, Hiratsuka T, Shinoki K, Iizumi T, Akamatsu T, Sakamoto C, Kobayashi M.
    Journal: J Gastroenterol; 2002; 37(3):164-71. PubMed ID: 11931528.
    Abstract:
    BACKGROUND: Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants given subsequently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment was involved in the prevention of subsequent ethanol-caused gastric injury in mice. METHODS: Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically determined every 8h. Mice were administered 95% ethanol 24h after the acidified ethanol pretreatment, and gastric mucosal damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage were also examined. RESULTS: Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with a peak level 24h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated histologically, irrespective of the pretreatment. CONCLUSIONS: Pretreatment-induced COX-2, in addition to COX-1, seemed to be involved in the defense mechanism through minimizing the damage caused by a subsequent irritant.
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