Tags

Type your tag names separated by a space and hit enter

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

Abstract

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Genomic Research Center for Gastroenterology, Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.

    , , , , , , ,

    Source

    Helicobacter 9:6 2004 Dec pg 632-42

    MeSH

    Apoptosis
    Catechin
    Cells, Cultured
    Enzyme Inhibitors
    Gastric Mucosa
    Glycosylation
    Helicobacter pylori
    Humans
    MAP Kinase Kinase 2
    Membrane Glycoproteins
    Mitogen-Activated Protein Kinase 3
    NF-kappa B
    Receptors, Cell Surface
    Signal Transduction
    Toll-Like Receptor 4
    Toll-Like Receptors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15610077

    Citation

    Lee, Kee-Myung, et al. "Protective Mechanism of Epigallocatechin-3-gallate Against Helicobacter Pylori-induced Gastric Epithelial Cytotoxicity Via the Blockage of TLR-4 Signaling." Helicobacter, vol. 9, no. 6, 2004, pp. 632-42.
    Lee KM, Yeo M, Choue JS, et al. Protective mechanism of epigallocatechin-3-gallate against Helicobacter pylori-induced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling. Helicobacter. 2004;9(6):632-42.
    Lee, K. M., Yeo, M., Choue, J. S., Jin, J. H., Park, S. J., Cheong, J. Y., ... Hahm, K. B. (2004). Protective mechanism of epigallocatechin-3-gallate against Helicobacter pylori-induced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling. Helicobacter, 9(6), pp. 632-42.
    Lee KM, et al. Protective Mechanism of Epigallocatechin-3-gallate Against Helicobacter Pylori-induced Gastric Epithelial Cytotoxicity Via the Blockage of TLR-4 Signaling. Helicobacter. 2004;9(6):632-42. PubMed PMID: 15610077.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Protective mechanism of epigallocatechin-3-gallate against Helicobacter pylori-induced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling. AU - Lee,Kee-Myung, AU - Yeo,Marie, AU - Choue,Jung-Sun, AU - Jin,Joo-Hyun, AU - Park,Soo Jin, AU - Cheong,Jae-Youn, AU - Lee,Kwang Jae, AU - Kim,Jin-Hong, AU - Hahm,Ki-Baik, PY - 2004/12/22/pubmed PY - 2005/5/17/medline PY - 2004/12/22/entrez SP - 632 EP - 42 JF - Helicobacter JO - Helicobacter VL - 9 IS - 6 N2 - 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. SN - 1083-4389 UR - https://www.unboundmedicine.com/medline/citation/15610077/Protective_mechanism_of_epigallocatechin_3_gallate_against_Helicobacter_pylori_induced_gastric_epithelial_cytotoxicity_via_the_blockage_of_TLR_4_signaling_ L2 - https://doi.org/10.1111/j.1083-4389.2004.00281.x DB - PRIME DP - Unbound Medicine ER -