RRC ID 42822
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