Helicobacter pylori activates NF-κB via the alternative pathway in B lymphocytes
Helicobacter pylori activates NF-κB via the alternative pathway in B lymphocytes
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DOI：
10.4049/jimmunol.175.11.7162
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发表时间：
2005-12-01
影响因子：
4.4
通讯作者：
Omata, M
中科院分区：
文献类型：
--
作者：
Ohmae, T;Hirata, Y;Omata, M
幽门螺杆菌可引起包括胃MALT淋巴瘤在内的多种胃十二指肠疾病，但其致病机制尚不清楚。幽门诱导的贲门发生是未知的。NF-κ B活化的替代途径涉及NF-κ B2/p100到p52的加工，与淋巴细胞存活、减弱的凋亡和次级淋巴组织发育有关。在这项研究中，我们调查了H。在B淋巴细胞中通过旁路途径，幽门螺杆菌诱导的NF-κ B活化。在inummoblot和EMSA中，H. pylori诱导NF-κ B2/p100加工为p52，随后在IM-9（人B细胞系）细胞和人外周血B细胞中核积累，但在AGS（人胃癌细胞系）细胞中不诱导。旁路途径的激活是LPS依赖的，而不是cag致病岛依赖的。旁路途径激活H。pylori感染与细胞凋亡减弱有关。在共培养的人B细胞和感染的人胃粘膜中，B淋巴细胞趋化因子、EBI-1配体趋化因子和基质细胞衍生因子-1 α mRNA的表达水平上调。在感染粘膜中，NF-κ B2/p100和p52在淋巴细胞的胞浆和核区室中被免疫组化检测到，而在上皮细胞中未检测到。综上所述，H. pylori激活B淋巴细胞中的NF-κ B通路。研究了H. pylori诱导的NF-κ B2/p100到p52的加工可能驱使淋巴细胞获得恶性潜能。
Helicobacter pylori causes various gastroduodenal diseases including gastric MALT lymphoma, but the mechanism underlying H. pylori-induced carchiogenesis is not known. The alternative pathway for NF-kappa B activation, which involves the processing of NF-kappa B2/p100 to p52, has been implicated in lymphocyte survival, attenuated apoptosis, and secondary lymphoid tissue development. In this study, we investigated H. pylori-induced activation of NF-kappa B through the alternative pathway in B lymphocytes. In inummoblot and EMSA, H. pylori induced NF-kappa B2/p100 processing to p52 and subsequent nuclear accumulation in IM-9 (human B cell line) cells and human peripheral blood B cells, but not in AGS (human gastric cancer cell line) cells. The activation of the alternative pathway was LPS-dependent but not cag pathogenicity island-dependent. Alternative pathway activation by H. pylori was associated with attenuated apoptosis. The expression levels of B lymphocyte chemoattractant, EBI-1 ligand chemokine, and stromal cell-derived factor-1 alpha mRNAs were up-regulated in cocultured human B cells and in infected human gastric mucosa. In the infected mucosa, NF-kappa B2/p100 and p52 were detected inummohistochemically in the cytoplasm and nuclear compartments of lymphocytes, but not in epithelial cells. In summary, H. pylori activates the alternative NF-kappa B pathway in B lymphocytes. The effects on chemokine production and antiapoptosis mediated by H. pylori-induced processing of NF-kappa B2/p100 to p52 may drive lymphocytes to acquire malignant potential.