TLR4, a member of pattern recognition receptors, is the main receptor of LPS. MD-2 physically associates with TLR4 on the cell surface and confers LPS responsiveness. Helicobacter pylori LPS is one of the major virulence factors for induction of gastritis. We demonstrated in this study the role of MD-2 in TLR4-dependent signaling in H. pylori-associated gastritis. Gastric biopsy samples collected from patients with and without H. pylori infection and four gastric cancer cell lines were used for this study. TLR-4 and MD-2 expression in biopsy specimens and the cell lines was examined by using RT-PCR. Localization of TLR-4 in histological sections was evaluated by immunohistochemistry. For in vitro functional assays, we established stable transfectants of AGS cells expressing TLR4 and MD-2. Cellular distribution of TLR4 was examined by flow cytometry. NF-κB activation and activation of IL-8 and MD-2 promoters were assessed by reporter gene assay. H. pylori infection up-regulated the TLR4 and MD-2 expression in gastric mucosa. TLR4 staining was observed predominantly in epithelial cells, located in both the cytoplasm and at the apical surface. MD-2 transfection in AGS cells markedly increased cell surface expression of TLR4 and augmented the activation of NF-κB and IL-8 promoter upon stimulation with H. pylori LPS. Live H. pylori also stimulated transcriptional activation of MD-2. This study revealed that MD-2 expression is elevated in gastric epithelial cells during H. pylori infection, suggesting that the TLR4/MD-2 system is a potent receptor complex involved in the response to H. pylori LPS in the stomach.
The present study showed for the first time that Reg protein may be a potent stimulator of gastric epithelial cells in H. pylori-infected human gastric mucosa stimulated by IL-8. Further, our findings provide evidence of a novel link between Reg protein and H. pylori infection, which may help explain the molecular mechanisms underlying H. pylori-associated diseases, including gastric cancer.
The combination of crystal violet chromoendoscopy and pit pattern diagnosis is considered to be useful for the surveillance of short-segment Barrett's esophagus.
A 26-year-old man underwent cardiac catheterization because of abnormal electrocardiography (QS in leads V 1 to V 3 ) and thallium stress scintigraphy (a fixed defect in the anteroseptal wall). The patient had a history of suspected Kawasaki disease with sudden cardiac arrest at the age of 1 year. Coronary angiography showed no significant aneurysm, occlusion, or stenosis but a mild dilatation with a braid-like appearance at the proximal segment of the left anterior descending artery (LAD) (Figure 1). Intravascular ultrasound (IVUS) revealed that this segment was composed of multiple channels. The channels were connected to the septal branch, the diagonal branch, and the distal LAD (Figure 2), suggesting spontaneous recanalization of the thrombotic LAD occlusion due to coronary vasculitis with Kawasaki disease. This lotus root-like appearance detected in vivo by IVUS presumably corresponds to the "arteries within the artery" phenomenon reported in a previous pathological study of Kawasaki disease.
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