Protective mechanism of epigallocatechin-3-gallate against Helicobacter pylori-induced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling

Kee-Myung Lee, Marie Yeo, Jung-Sun Choue, Joo-Hyun Jin, Soo Jin Park, Jae-Youn Cheong, Kwang Jae Lee, Jin-Hong Kim, Ki-Baik Hahm
Helicobacter 2004, 9 (6): 632-42

BACKGROUND: Helicobacter pylori infection leads to gastric mucosal damage by several mechanisms including the direct effect of virulence factors produced by H. pylori, propagation of inflammation, oxidative stress, DNA damage, and induction of apoptosis. (-)-Epigallocatechin-3-gallate (EGCG), one of the green tea catechins, is known to suppress H. pylori-induced gastritis through its antioxidative and antibacterial actions. In this study, we evaluated the protective mechanism of EGCG against H. pylori-induced cytotoxicity in gastric epithelial cells.

MATERIALS AND METHODS: MTT assays and dye exclusion assays were performed to analyze the effect of EGCG on the viability of gastric epithelial cells. The degree of DNA damage was evaluated by Comet assay and apoptotic DNA fragmentation assay. To investigate the effect of EGCG on H. pylori-induced toll-like receptor 4 (TLR-4) signaling, reverse transcription-polymerase chain reaction and Western blot analysis corresponding to glycosylated TLR-4 were carried out. Lipoxygenase metabolites were measured with reverse-phase, high-performance liquid chromatography.

RESULTS: EGCG pretreatment effectively rescued gastric mucosal cells from the H. pylori-induced apoptotic cell death and DNA damage, and administration of this catechin enhanced gastric epithelial cell proliferation. Helicobacter pylori infection stimulated the glycosylation of TLR-4, which initiates intracellular signaling in the infected host cell, but the pretreatment with EGCG completely blocked the TLR-4 glycosylation. The blockage of TLR-4 activation by EGCG resulted in inactivation of extracellular signal response kinase 1/2 and of nuclear factor-kappaB, the downstream molecules of TLR-4 signaling induced by H. pylori. This disturbance of H. pylori-induced host cell signaling by EGCG attenuated the synthesis of the proinflammatory mediator, hydroxyeicosatetraenoic acid.

CONCLUSIONS: EGCG pretreatment showed significant cytoprotective effects against H. pylori-induced gastric cytotoxicity via interference of the TLR-4 signaling induced by H. pylori. Thus, our result implies that continuous intakes of green tea could prevent the deleterious consequences of H. pylori infection.

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