Neisseria gonorrhoeae epithelial cell interaction leads to the activation of the transcription factors nuclear factor kappaB and activator protein 1 and the induction of inflammatory cytokines.
Neisseria gonorrhoeae epithelial cell interaction leads to the activation of the transcription factors nuclear factor kappaB and activator protein 1 and the induction of inflammatory cytokines.
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DOI：
10.1084/jem.186.2.247
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发表时间：
1997-07-21
期刊：
影响因子：
--
通讯作者：
Meyer TF
中科院分区：
文献类型：
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作者：
Naumann M;Wessler S;Bartsch C;Wieland B;Meyer TF
我们研究了人类细菌病原体淋病奈瑟菌 (Ngo) 对上皮细胞感染后核因子 (NF)-κB 激活和炎症细胞因子基因转录激活的影响。在感染过程中，淋病病原体 Ngo 粘附并穿透粘膜上皮细胞。在体内，局部淋球菌感染通常与大量炎症反应相关。我们观察到 Ngo 感染的上皮细胞中几种炎症细胞因子信使 RNA (mRNA) 的上调和蛋白质的释放。此外，Ngo感染诱导了NF-κB DNA-蛋白质复合物的形成，并且随着时间的延迟，激活蛋白1被激活，而与cAMP反应元件或CAAT/增强子结合蛋白DNA结合位点结合的碱性亮氨酸拉链转录因子则没有被激活。在使用 NF-κB 特异性抗体的 Supershift 测定中，我们鉴定了 NF-κB p50/p65 异二聚体。 NF-κB复合物在感染后10分钟内形成，并在感染后90分钟减少。肿瘤坏死因子 α 和白细胞介素 (IL)-1β 的合成发生在较晚的时间，因此不能解释 NF-κB 的激活。对瞬时转染的 IL-6 启动子缺失构建体的分析表明，NF-κB 对于 Ngo 感染后 IL-6 启动子的转录激活起着至关重要的作用。蛋白酶抑制剂 N-甲苯磺酰基-L-苯丙氨酸氯甲基酮使 NF-κB 失活，抑制大多数（但不是全部）研究的细胞因子基因的 mRNA 上调。用细胞松弛素 D 处理的 Ngo 感染的上皮细胞中也发生了 NF-κB 的激活和细胞因子 mRNA 的上调，表明在入侵之前诱导了细胞外信号传导。
We have studied the effect of human bacterial pathogen Neisseria gonorrhoeae (Ngo) on the activation of nuclear factor (NF)-κB and the transcriptional activation of inflammatory cytokine genes upon infection of epithelial cells. During the course of infection, Ngo, the etiologic agent of gonorrhea, adheres to and penetrates mucosal epithelial cells. In vivo, localized gonococcal infections are often associated with a massive inflammatory response. We observed upregulation of several inflammatory cytokine messenger RNAs (mRNAs) and the release of the proteins in Ngo-infected epithelial cells. Moreover, infection with Ngo induced the formation of a NF-κB DNA–protein complex and, with a delay in time, the activation of activator protein 1, whereas basic leucine zipper transcription factors binding to the cAMP-responsive element or CAAT/enhancer-binding protein DNA-binding sites were not activated. In supershift assays using NF-κB–specific antibodies, we identified a NF-κB p50/p65 heterodimer. The NF-κB complex was formed within 10 min after infection and decreased 90 min after infection. Synthesis of tumor necrosis factor α and interluekin (IL)-1β occurred at later times and therefore did not account for NF-κB activation. An analysis of transiently transfected IL-6 promoter deletion constructs suggests that NF-κB plays a crucial role for the transcriptional activation of the IL-6 promoter upon Ngo infection. Inactivation of NF-κB conferred by the protease inhibitor N-tosyl-l-phenylalanine chloromethyl ketone inhibited mRNA upregulation of most, but not all, studied cyctokine genes. Activation of NF-κB and cytokine mRNA upregulation also occur in Ngo-infected epithelial cells that were treated with cytochalasin D, indicating an extracellular signaling induced before invasion.