Shimada T, Watanabe N, Ohtsuka Y, Endoh M, Kojima K, Hiraishi H, Terano A
Second Department of Internal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
J Pharmacol Exp Ther. 1999 Oct;291(1):345-52.
Gastric epithelial chemokine response is a primary factor in the induction of gastric inflammation associated with Helicobacter pylori infection. Because sustained inflammation is a risk for gastric mucosal damage, agents that down-regulate inflammatory responses may be of therapeutic significance. We examined the effect of polaprezinc, a potent antiulcer agent, on proinflammatory cytokine-induced interleukin (IL)-8 expression in gastric epithelial cells. Because IL-8 expression is regulated by the transcription factor nuclear factor-kappaB (NF-kappaB), we also examined the effect of polaprezinc on NF-kappaB activity. MKN28 cells were used as a model of gastric epithelial cells. Secreted IL-8 was quantified by IL-8 specific enzyme-linked immunosorbent assay, and IL-8 mRNA expression was examined by Northern blot analysis. NF-kappaB activity was analyzed by electrophoretic mobility shift assay. Western blot analysis with anti-phospho-IkappaB-alpha antibody was performed to assess IkappaB-alpha phosphorylation. Polaprezinc-suppressed IL-8 secretion induced by tumor necrosis factor alpha (TNF-alpha) or IL-1beta in a dose-dependent manner. IL-8 mRNA expression also was inhibited by polaprezinc. NF-kappaB activation in response to TNF-alpha, IL-1beta, phorbol ester, and H(2)O(2) was down-regulated by polaprezinc. Western blot analysis showed inhibition of TNF-alpha-induced IkappaB-alpha phosphorylation in the presence of polaprezinc. Collectively, these results suggest that polaprezinc is a novel type of anti-inflammatory agent that down-regulates inflammatory responses of gastric mucosal cells.
胃上皮趋化因子反应是幽门螺杆菌感染相关胃炎症诱导中的一个主要因素。由于持续炎症是胃黏膜损伤的一个风险因素，下调炎症反应的药物可能具有治疗意义。我们研究了强效抗溃疡药物聚普瑞锌对促炎细胞因子诱导的胃上皮细胞白细胞介素（IL）-8表达的影响。由于IL-8的表达受转录因子核因子-κB（NF-κB）调控，我们还研究了聚普瑞锌对NF-κB活性的影响。采用MKN28细胞作为胃上皮细胞模型。通过IL-8特异性酶联免疫吸附测定法定量分泌的IL-8，并通过Northern印迹分析检测IL-8 mRNA表达。通过电泳迁移率变动分析来分析NF-κB活性。用抗磷酸化IκB-α抗体进行蛋白质印迹分析以评估IκB-α磷酸化。聚普瑞锌以剂量依赖方式抑制肿瘤坏死因子α（TNF-α）或IL-1β诱导的IL-8分泌。聚普瑞锌也抑制IL-8 mRNA表达。聚普瑞锌下调了对TNF-α、IL-1β、佛波酯和H2O2的NF-κB激活。蛋白质印迹分析显示在有聚普瑞锌存在的情况下TNF-α诱导的IκB-α磷酸化受到抑制。总体而言，这些结果表明聚普瑞锌是一种新型抗炎药物，可下调胃黏膜细胞的炎症反应。
