Vol. 291, Issue 1, 345-352, October 1999

Polaprezinc Down-Regulates Proinflammatory Cytokine-Induced Nuclear Factor-B Activiation and Interleukin-8 Expression in Gastric Epithelial Cells¹

Tadahito Shimada, Naomi Watanabe, Yukio Ohtsuka, Motoya Endoh, Kazuo Kojima, Hideyuki Hiraishi and Akira Terano

Second Department of Internal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi, Japan

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-B (NF-B), we also examined the effect of polaprezinc on NF-B 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-B activity was analyzed by electrophoretic mobility shift assay. Western blot analysis with anti-phospho-IB- antibody was performed to assess IB- phosphorylation. Polaprezinc-suppressed IL-8 secretion induced by tumor necrosis factor  (TNF-) or IL-1 in a dose-dependent manner. IL-8 mRNA expression also was inhibited by polaprezinc. NF-B activation in response to TNF-, IL-1, phorbol ester, and H₂O₂ was down-regulated by polaprezinc. Western blot analysis showed inhibition of TNF--induced IB- 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.