Tumor necrosis factor alpha and interleukin 1β up-regulate gastric mucosal Fas antigen expression in Helicobacter pylori infection
Tumor necrosis factor alpha and interleukin 1β up-regulate gastric mucosal Fas antigen expression in Helicobacter pylori infection
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DOI：
10.1128/iai.68.3.1189-1195.2000
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发表时间：
2000-03-01
影响因子：
3.1
通讯作者：
Korah, RM
中科院分区：
文献类型：
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作者：
Houghton, J;Macera-Bloch, LS;Korah, RM
Fas介导的胃粘膜细胞凋亡作为幽门螺杆菌感染引起的组织损伤的一个原因正受到人们的关注。我们直接探讨了幽门螺杆菌对未转化的胃粘膜细胞系(RGM-1)Fas介导的细胞凋亡的影响，以及感染后建立的炎症环境的影响。暴露于幽门螺杆菌激活的外周血单个核细胞(PBMC)，而不是幽门螺杆菌本身，可诱导Fas抗原(Fas Ag)的表达，表明该系统对炎性细胞因子具有Fas调节作用。在所测试的各种炎性细胞因子中，只有白细胞介素1β和肿瘤坏死因子α诱导Fas抗原的表达，从条件培养液中去除这两种因子中的任何一种都会取消这种反应。有趣的是，当暴露在Fas配体下时，用PBMC条件培养液处理的RGM-1细胞经历了大量和快速的细胞死亡，早期对细胞总数的影响很小。细胞周期分析显示，暴露于Fas配体的细胞中，S期细胞显著增加，提示其增殖反应增强。综上所述，这些数据表明，幽门螺杆菌感染后的免疫环境在启动胃粘膜细胞发生凋亡或增殖的过程中起着关键作用，这取决于它们的Fas抗原状态。
Fas-mediated gastric mucosal apoptosis is gaining attention as a cause of tissue damage due to Helicobacter pylori infection. We explored the effects of H. pylori directly, and the effects of the inflammatory environment established subsequent to H. pylori infection, on Fas-mediated apoptosis in a nontransformed gastric mucosal cell line (RGM-1). Exposure to H. pylori-activated peripheral blood mononuclear cells (PBMCs), but not H. pylori itself, induced Fas antigen (Fas Ag) expression, indicating a Fas-regulatory role for inflammatory cytokines in this system. Of various inflammatory cytokines tested, only interleukin 1 beta and tumor necrosis factor alpha induced Fas Ag expression, and removal of either of these from the conditioned medium abrogated the response. When exposed to Fas ligand, RGM-1 cells treated with PBMC-conditioned medium underwent massive and rapid cell death, interestingly, with a minimal effect on total cell numbers early on. Cell cycle analysis revealed a substantial increase in S phase cells among cells exposed to Fas ligand, suggesting an increase in their proliferative response. Taken together, these data indicate that the immune environment secondary to H. pylori infection plays a critical role in priming gastric mucosal cells to undergo apoptosis or to proliferate based upon their Fas Ag status.