Listeriolysin O secreted by Listeria monocytogenes induces NF-κB signalling by activating the IκB kinase complex
Listeriolysin O secreted by Listeria monocytogenes induces NF-κB signalling by activating the IκB kinase complex
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DOI：
10.1046/j.1365-2958.2002.02973.x
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发表时间：
2002-06-01
影响因子：
3.6
通讯作者：
Berche, P
中科院分区：
文献类型：
--
作者：
Kayal, S;Lilienbaum, A;Berche, P
李斯特菌溶血素 O (LLO) 是病原体单核细胞增生李斯特菌分泌的一种成孔溶细胞素，是其细胞内生存所必需的。我们最近证明在内皮细胞中，LLO 激活 NF-kappaB 信号通路。在这项工作中，我们使用广泛用于分析 NF-kappaB 激活信号通路的细胞模型，即人胚肾 HEK-293 细胞系及其衍生物（转染子或突变体），研究了 LLO 诱导的 NF-kappaB 激活的分子级联。当表达 IL-1RI 的稳定转染衍生 HEK-293 细胞暴露于 LLO 时，检测到强烈的 NF-kappaB 激活，与表达非常低水平的 IL-1RI 的其他细胞系（HEK-293 野生型、HEK-293.T 和 COS）形成对比。尽管 LLO 依赖性 NF-kappaB 激活的延迟动力学表明存在自分泌或旁分泌 IL-1 依赖性途径，但我们发现 LLO 依赖性 NF-kappaB 激活不需要 IL-1 蛋白合成，也不需要与 IL-1RI 特异性受体相互作用。在此，我们证明 LLO 依赖性 NF-kappaB 激活需要激活 IKK 复合物的 IkappaB 激酶 beta (IKKbeta) 亚基，以磷酸化和降解细胞质 IkappaBalpha（NF-kappaB 的天然抑制剂）。 LLO 诱导的激活不需要接头 MyD88 和 IL-1R 相关激酶 (IRAK)。我们认为 LLO 诱导了一条与 IL-1 及其受体不同的信号通路。
Listeriolysin O (LLO) is a pore-forming cytolysin secreted by the pathogen Listeria monocytogenes and is required for its intracellular survival. We recently demonstrated that in endothelial cells, LLO activates the NF-kappaB signalling pathway. In this work, we studied the LLO-induced molecular cascade of NF-kappaB activation with a cellular model extensively used to analyse the signalling pathway of NF-kappaB activation, i.e. the human embryonic kidney HEK-293 cell line and its derivatives (transfectants or mutants). When the stably transfected derivative HEK-293 cells expressing IL-1RI were exposed to LLO, a strong NF-kappaB activation was detected, contrasting with other cell lines (HEK-293 wild type, HEK-293.T and COS) expressing a very low level of IL-1RI. Although a delayed kinetics of LLO-dependent NF-kappaB activation suggests an autocrine or paracrine IL-1-dependent pathway, we found that LLO-dependent NF-kappaB activation did not require the IL-1 protein synthesis nor the interaction with the IL-1RI specific receptor. Herein, we demonstrated that LLO-dependent NF-kappaB activation requires the activation of the IkappaB kinase beta (IKKbeta) subunit of IKK complex to phosphorylate and degrade cytoplasmic IkappaBalpha, a natural inhibitor of NF-kappaB. The activation induced by LLO does not require the adapters MyD88 and IL-1R-associated kinase (IRAK). We suggested that LLO induces a distinct signalling pathway from that of IL-1 and its receptor.