Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20), gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC, n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-kappaB, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-kappaB activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant-negative mutants of NIK and various IkappaB kinase complexes, including IKKbeta (Y188F), IKKbeta (Y199F), and IKKbeta (FF), inhibited the COX-2 promoter activity. Phosphorylation of GST-IKKbeta (132-206) at Tyr188 and Tyr199 by c-Src was found after H. pylori infection. In summary, H. pylori induces COX-2 expression via activations of NF-kappaB, NF-interleukin 6, the cAMP response element. In NF-kappaB activation, H. pylori acts through TLR2/TLR9 to activate both the cascade of PI-PLCgamma/PKCalpha/c-Src/IKKalpha/beta and the cascade of NIK/IKKalpha/beta, resulting in the IkappaBalpha degradation and the expression of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in patients colonized with these strains.
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PMID:Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB activation. 1545 96

The aim of this study was to assess the significance of the interleukin 6 gene polymorphism -174 in gastric cancer risk. The interleukin 6 -174 G/C (rs1800795) gene polymorphisms was analyzed in gastric cancer, peptic ulcer, and nonulcer dyspepsia patients and in healthy control subjects and the data were correlated with the histopathological features of the patients' biopsies. The interleukin 6 -174 GG and GC genotypes have been previously associated with high interleukin 6 serum levels. We discovered that the interleukin 6 -174 GG and GC genotypes are associated with an increased risk of the diffuse histologic subtype of gastric carcinomas (OR: 6.809, P = 0.034), but absent in the intestinal type carcinomas (OR: 1.109, P = 0.908). No significant associations with peptic ulcer, gastric atrophy, or intestinal metaplasia were seen. Our results demonstrate that the interleukin 6 -174 GG and GC genotypes increase the risk of the diffuse type gastric carcinoma, but not the intestinal type gastric carcinoma or its precursor conditions, including atrophy or intestinal metaplasia. Thus, interleukin 6 seems to be an important carcinogenetic factor in the diffuse type gastric adenocarcinoma and its carcinogenetic effect could be noninflammatory.
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PMID:Interleukin 6 gene polymorphism -174 is associated with the diffuse type gastric carcinoma. 2389 9