Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells
Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells
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DOI：
10.1053/gast.1997.v113.pm9322504
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发表时间：
1997-10-01
期刊：
影响因子：
29.4
通讯作者：
Kelly, CP
中科院分区：
文献类型：
--
作者：
Keates, S;Hitti, YS;Kelly, CP
背景和目的：幽门螺杆菌粘附在胃上皮细胞上并刺激白细胞介素 (IL)-8 的产生，这可能有助于中性粒细胞浸润胃上皮细胞，从而表征幽门螺杆菌胃炎。本研究探讨了导致幽门螺杆菌诱导上皮细胞产生 IL-8 的分子机制。方法：对幽门螺杆菌的细胞和核提取物进行了 NF-κ B 的电泳迁移率变化分析。幽门螺杆菌感染的 AGS 和 Kato III 人胃上皮细胞。结果：幽门螺杆菌感染激活转录因子 NF-kappa B 并诱导 NF-kappa B p50/p65 异二聚体和 p50 同二聚体的核转位，NF-kappa B 核转位（30 分钟）后 IL-8 信使 RNA（1 小时）和蛋白质水平（4 小时）增加，这与 NF-kappa B 对 IL-8 基因转录的上调一致。 PDTC 可阻断 NF-kappa B 激活，可抑制幽门螺杆菌诱导的 IL-8 产量增加 90%。使用识别 p65 I-kappa B 结合区的单克隆抗体进行的免疫组织化学研究表明，幽门螺杆菌胃炎患者的胃上皮细胞中的 NF-kappa B 被激活。结论：幽门螺杆菌感染在体外和体内激活胃上皮细胞中的 NF-kappa B。 NF-κB是IL-8产生的转录调节因子，其在细菌感染后的激活可能是胃肠道上皮细胞的重要防御反应。
Background & Aims: Helicobacterpylori adheres to gastric epithelial cells and stimulates interleukin (IL)-8 production, This may be instrumental in neutrophil infiltration of the gastric epithelium that characterizes H. pylori gastritis, This study examined the molecular mechanisms leading to H. pylori-induced epithelial cell IL-8 production, Methods: Electrophoretic mobility shift analyses for NF-kappa B were performed on cell and nuclear extracts from H. pylori-infected AGS and Kato III human gastric epithelial cells. Results: H. pylori infection activated the transcription factor NF-kappa B and induced nuclear translocation of both NF-kappa B p50/p65 heterodimers and p50 homodimers, Nuclear translocation of NF-kappa B (30 minutes) was followed by increased IL-8 messenger RNA (1 hour) and protein levels (4 hours) consistent with NF-kappa B up-regulation of IL-8 gene transcription, Pretreatment of AGS cells with PDTC, which blocks NF-kappa B activation, inhibited H. pylori-induced increases in IL-8 production by 90%. Immunohistochemical studies using a monoclonal antibody that recognizes the I-kappa B binding region of p65 showed activated NF-kappa B in gastric epithelial cells of patients with H. pylori gastritis, Conclusions: H. pylori infection activates NF-kappa B in gastric epithelial cells in vitro and in vivo. NF-kappa B is a transcriptional regulator of IL-8 production, and its activation after bacterial infection may be an important defense response in gastrointestinal epithelial cells.