Helicobacter pylori에의해 호중구 및 위점막 셰포로부터 유도되는 LeukotrieneB4의 생성에 미치는 Rebamipide의 영향

The Effect of Rebamipide on Cellular Release of Leukotriene B4 by Helicobacter Pylor

Leukotrienes(LTs) are known to act as a mediator provoking tissue r‘esponse in inflammation. This finding implicates that LTs also play important roles in the pathogenesis of H. pylori-induced gastritis and gastric ulceration. Rebamipide is being currently used as a therapeutics for gastritis and peptic ulcer， but their mechanisms of action have not been known clearly yet. One possibility is that their therapeutic effects are ascribed to interfering with the H. pylori-induced release of LTs from neutrophils and gastric mucosal cells. In the present study， this possibility was tested using LTB4 as the test material in human neutrophils and Kato III cells(gastric adenoma cells as a substitute for gastric mucosal cells). The release of LTB4 from both neutrophils and Kato III cells was time and H. pylori-dose dependent. The maximum release of LTB4 was induced by neutrophils and Kato III cells when these cells incubated with H. pylori 4.8 X 108 cellsjml for 30min. But in the presence of rebamipide the release of LTB4 from these cells was suppressed in dose dependent manners. The release was completely suppressed at 1.0 mM of rebamipide in neutrophils and 2.0 mM of this drug in Kato III cells， respectively. We also obtained the resu1ts that the 2+ release of LTB4 was induced by A23187(Ca2+ ionophore) and the A23187-induced release was also inhibited by rebamipide. It seems that the machanism of action of rebamipide is through its interaction with the level of intracellular Ca2+. In view of the roles of LTB4 in inflammatory reaction and the roles of H. pylori in gastritis and peptic ulcer， the effects of this drug observed in this study may contribute to their therapeutic action in these gastric disorders.