Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis
Cryptosporidium parvum activates nuclear factor κB in biliary epithelia preventing epithelial cell apoptosis
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DOI：
10.1053/gast.2001.24850
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发表时间：
2001-06-01
期刊：
影响因子：
29.4
通讯作者：
LaRusso, NF
中科院分区：
文献类型：
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作者：
Chen, XM;Levine, SA;LaRusso, NF
（背景与目的）：我们之前的研究表明，小隐孢子虫在体内诱导胆道上皮细胞凋亡，并在体外诱导未感染的旁观者胆道上皮细胞凋亡。我们分析了小弧菌诱导的核因子κ B （nf - κ B）在人胆道上皮细胞中的激活，并评估了其与上皮细胞凋亡的相关性。（方法）bar下：采用隐孢子虫感染人胆道上皮细胞系的体外模型，检测C. parvum诱导的NF-kappaB活化和相关凋亡。（结果）bar下：在直接暴露于C. parvum的胆道上皮细胞培养中，观察到I -kappaB降解和NF-kappaB家族蛋白（p65和p50）的核易位。NF-kappaB活化仅在直接感染的细胞中发现（而在旁观者未感染的细胞中没有发现）。从感染细胞培养物中检测到已知NF-kappaB基因产物白细胞介素8的时间依赖性分泌。相比之下，抑制NF-kappaB激活导致直接感染的细胞凋亡，并显著增强了C. parvum诱导的未感染的细胞凋亡。（结论）在bar下：这些观察结果支持了这样的概念，即虽然小孢子虫在未感染的旁观者胆道上皮细胞中触发宿主细胞凋亡，从而可能限制感染的传播，但它直接激活被感染胆道上皮中的NF-kappaB/I kappaB系统，从而保护被感染细胞免于死亡，促进寄生虫的生存和繁殖。
(Background & Aims) under bar: Our previous studies have shown that Cryptosporidium parvum induces biliary epithelial cell apoptosis in vivo and causes apoptosis in bystander uninfected biliary epithelia in vitro. We analyzed C. parvum-induced nuclear factor kappa B (NF-kappaB) activation in human biliary epithelial cells and assessed its relevance to epithelial cell apoptosis. (Methods) under bar: In vitro models of cryptosporidial infection using a human biliary epithelial cell line were used to assay C. parvum-induced NF-kappaB activation and associated apoptosis, (Results) under bar: Degradation of I kappaB and nuclear translocation of the NF-kappaB family of proteins (p65 and p50) were observed in the biliary epithelial cell cultures directly exposed to the parasite. Activation of NF-kappaB was found only in directly infected cells (but not in bystander uninfected cells). A time-dependent secretion of a known NF-kappaB gene product, interleukin 8, from infected cell cultures was detected. C. parvum-induced biliary epithelial cell apoptosis was limited to bystander uninfected cells, In contrast, inhibition of NF-kappaB activation resulted in apoptosis in directly infected cells and significantly enhanced C. parvum-induced apoptosis in bystander uninfected cells. (Conclusions) under bar: These observations support the concept that, while C. parvum triggers host cell apoptosis in bystander uninfected biliary epithelial cells, which may limit spread of the infection, it directly activates the NF-kappaB/I kappaB system in infected biliary epithelia thus protecting infected cells from death and facilitating parasite survival and propagation.