TY - JOUR T1 - Polaprezinc Down-Regulates Proinflammatory Cytokine-Induced Nuclear Factor-κB Activiation and Interleukin-8 Expression in Gastric Epithelial Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 345 LP - 352 VL - 291 IS - 1 AU - Tadahito Shimada AU - Naomi Watanabe AU - Yukio Ohtsuka AU - Motoya Endoh AU - Kazuo Kojima AU - Hideyuki Hiraishi AU - Akira Terano Y1 - 1999/10/01 UR - http://jpet.aspetjournals.org/content/291/1/345.abstract N2 - 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-κB (NF-κB), we also examined the effect of polaprezinc on NF-κB 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-κB activity was analyzed by electrophoretic mobility shift assay. Western blot analysis with anti-phospho-IκB-α antibody was performed to assess IκB-α phosphorylation. Polaprezinc-suppressed IL-8 secretion induced by tumor necrosis factor α (TNF-α) or IL-1β in a dose-dependent manner. IL-8 mRNA expression also was inhibited by polaprezinc. NF-κB activation in response to TNF-α, IL-1β, phorbol ester, and H2O2 was down-regulated by polaprezinc. Western blot analysis showed inhibition of TNF-α-induced IκB-α 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. The American Society for Pharmacology and Experimental Therapeutics ER -