PT  - JOURNAL ARTICLE
AU  - Shimada, Tadahito
AU  - Watanabe, Naomi
AU  - Ohtsuka, Yukio
AU  - Endoh, Motoya
AU  - Kojima, Kazuo
AU  - Hiraishi, Hideyuki
AU  - Terano, Akira
TI  - Polaprezinc Down-Regulates Proinflammatory Cytokine-Induced Nuclear Factor-κB Activiation and Interleukin-8 Expression in Gastric Epithelial Cells
DP  - 1999 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 345--352
VI  - 291
IP  - 1
4099  - http://jpet.aspetjournals.org/content/291/1/345.short
4100  - http://jpet.aspetjournals.org/content/291/1/345.full
SO  - J Pharmacol Exp Ther1999 Oct 01; 291
AB  - 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