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標題: Ceramide and Toll-Like Receptor 4 Are Mobilized into Membrane Rafts in Response to Helicobacter pylori Infection in Gastric Epithelial Cells
作者: Lu, D.Y.
Chen, H.C.
Yang, M.S.
Hsu, Y.M.
Lin, H.J.
Tang, C.H.
Lee, C.H.
Lai, C.K.
Lin, C.J.
Shyu, W.C.
Lin, F.Y.
Lai, C.H.
關鍵字: nf-kappa-b;glycosylphosphatidylinositol-anchored proteins;lipid rafts;vacuolating cytotoxin;signal-transduction;innate immunity;cancer-cells;ags cells;expression;tlr4
Project: Infection and Immunity
期刊/報告no:: Infection and Immunity, Volume 80, Issue 5, Page(s) 1823-1833.
Helicobacter pylori infection is thought to be involved in the development of several gastric diseases. Two H. pylori virulence factors (vacuolating cytotoxin A and cytotoxin-associated gene A) reportedly interact with lipid rafts in gastric epithelial cells. The role of Toll-like receptor (TLR)-mediated signaling in response to H. pylori infection has been investigated extensively in host cells. However, the receptor molecules in lipid rafts that are involved in H. pylori-induced innate sensing have not been well characterized. This study investigated whether lipid rafts play a role in H. pylori-induced ceramide secretion and TLR4 expression and thereby contribute to inflammation in gastric epithelial cells. We observed that both TLR4 and MD-2 mRNA and protein levels were significantly higher in H. pylori-infected AGS cells than in mock-infected cells. Moreover, significantly more TLR4 protein was detected in detergent-resistant membranes extracted from H. pylori-infected AGS cells than in those extracted from mock-infected cells. However, this effect was attenuated by the treatment of cells with cholesterol-usurping agents, suggesting that H. pylori-induced TLR4 signaling is dependent on cholesterol-rich microdomains. Similarly, the level of cellular ceramide was elevated and ceramide was translocated into lipid rafts after H. pylori infection, leading to interleukin-8 (IL-8) production. Using the sphingomyelinase inhibitor imipramine, we observed that H. pylori-induced TLR4 expression was ceramide dependent. These results indicate the
ISSN: 0019-9567
DOI: 10.1128/iai.05856-11
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