論文 - 詳細
RRC ID | 42822 |
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著者 | Handa O, Yoshida N, Fujita N, Tanaka Y, Ueda M, Takagi T, Kokura S, Naito Y, Okanoue T, Yoshikawa T. |
タイトル | Molecular mechanisms involved in anti-inflammatory effects of proton pump inhibitors. |
ジャーナル | Inflamm Res |
Abstract |
OBJECTIVE:Interleukin (IL)-8 has been reported to participate in neutrophil infiltration in Helicobacter pylori (H. pylori)-induced gastritis in humans. In this study, we investigated the anti-inflammatory actions beyond the suppression of acid secretion by proton pump inhibitors (PPI), such as omeprazole and lansoprazole, on IL-8 production by gastric epithelial cells (MKN45) and human umbilical vein endothelial cells (HUVEC) and on the transendothelial migration of polymorphonuclear neutrophils (PMN). MATERIALS AND METHODS:MKN45 and HUVEC were stimulated with H. pylori water extract (HPE) and IL-1beta, respectively, and nuclear factor kappa B (NFkappaB) activation and subsequent IL-8 production was assessed in the absence or presence of PPI. We also assessed the effect of PPI on IL-8-induced PMN transendothelial migration and on the alteration of cytoplasmic calcium concentration in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMN. RESULTS:HPE and IL-1beta induced a significant increase in IL-8 production by MKN45 and HUVEC, respectively, along with NFkappaB activation, which was significantly inhibited by PPI. PPI also inhibited the IL-8-induced transendothelial migration of PMN and the fMLP-induced cytosolic calcium increase in PMN. CONCLUSIONS:PPI attenuate PMN-dependent gastric mucosal inflammation partly by interfering with NFkappaB activation in vascular endothelial cells and gastric epithelial cells, and partly by modulating the calcium concentration of PMN. |
巻・号 | 55(11) |
ページ | 476-80 |
公開日 | 2006-11-1 |
DOI | 10.1007/s00011-006-6056-4 |
PMID | 17122965 |
MeSH | 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacology Anti-Inflammatory Agents / pharmacology* Calcium / metabolism Cell Line, Tumor Cell Movement / drug effects* Cells, Cultured Endothelium, Vascular / cytology Endothelium, Vascular / drug effects Endothelium, Vascular / metabolism Enzyme Inhibitors / pharmacology* Epithelium / metabolism Epithelium / pathology Humans Interleukin-8 / metabolism* Lansoprazole Ligases / metabolism NF-kappa B / metabolism Neutrophils / cytology Neutrophils / drug effects Omeprazole / pharmacology Proton Pump Inhibitors* Stomach Neoplasms / metabolism Stomach Neoplasms / pathology |
IF | 3.174 |
引用数 | 65 |
WOS 分野 | IMMUNOLOGY CELL BIOLOGY |
リソース情報 | |
ヒト・動物細胞 |