Vimentin and PSF act in concert to regulate IbeA+ E. coli K1 induced activation and nuclear translocation of NF-κB in human brain endothelial cells.
Vimentin and PSF act in concert to regulate IbeA+ E. coli K1 induced activation and nuclear translocation of NF-κB in human brain endothelial cells.
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DOI：
10.1371/journal.pone.0035862
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Huang SH
中科院分区：
文献类型：
--
作者：
Chi F;Bo T;Wu CH;Jong A;Huang SH
IbeA 通过其主要受体波形蛋白及其辅助受体 PSF 诱导 NF-κB 信号传导，是脑膜炎大肠杆菌 K1 渗透和白细胞跨血脑屏障 (BBB) 迁移所必需的，这是细菌性脑膜炎的标志。然而，波形蛋白和 PSF 如何协同促进 IbeA 诱导的细胞质激活和 NF-κB 核转位（这是细菌介导的致病性所必需的）尚不清楚。 IbeA 诱导的大肠杆菌 K1 入侵、多形核白细胞 (PMN) 迁移和 IKK/NF-κB 激活可被 NF-κB 抑制剂咖啡酸苯乙酯 (CAPE) 阻断。 IKKα/β 磷酸化被 ERK 抑制剂阻断。免疫共沉淀分析表明，波形蛋白与静息细胞中的 IκB、NF-κB 和微管蛋白形成复合物。 IbeA 可以以时间依赖性方式诱导该复合物的解离以及 PSF 与 NF-κB 的同时结合。波形蛋白的头部结构域是复合物形成所必需的。波形蛋白丝和微管这两种细胞骨架成分有助于 NF-κB 的调节。 SiRNA 介导的敲低研究表明，在缺乏波形蛋白和 PSF 的 HBMEC 中，IKKα/β 磷酸化被完全消除。 ERK 的磷酸化和 NF-κB 的核转位完全依赖于 PSF。这些发现表明波形蛋白和 PSF 共同促进 IbeA 诱导的细胞质激活和 NF-κB 激活的核转位。 PSF 对于 NF-κB 和 ERK 易位至细胞核至关重要。这些发现揭示了 IbeA 结合蛋白以前未被认识到的方面。波形蛋白和 PSF 对 IbeA 诱导的细胞质激活和 NF-κB 核转位的协同作用可能代表了病原体诱导的信号转导的新范例，并导致预防和治疗细菌性脑膜炎的新策略的发展。
IbeA-induced NF-κB signaling through its primary receptor vimentin as well as its co-receptor PSF is required for meningitic E. coli K1 penetration and leukocyte transmigration across the blood-brain barrier (BBB), which are the hallmarks of bacterial meningitis. However, it is unknown how vimentin and PSF cooperatively contribute to IbeA-induced cytoplasmic activation and nuclear translocation of NF-κB, which are required for bacteria-mediated pathogenicities. IbeA-induced E. coli K1 invasion, polymorphonuclear leukocyte (PMN) transmigration and IKK/NF-κB activation are blocked by Caffeic acid phenethyl ester (CAPE), an inhibitor of NF-κB. IKKα/β phosphorylation is blocked by ERK inhibitors. Co-immunoprecipitation analysis shows that vimentin forms a complex with IκB, NF-κB and tubulins in the resting cells. A dissociation of this complex and a simultaneous association of PSF with NF-κB could be induced by IbeA in a time-dependent manner. The head domain of vimentin is required for the complex formation. Two cytoskeletal components, vimentin filaments and microtubules, contribute to the regulation of NF-κB. SiRNA-mediated knockdown studies demonstrate that IKKα/β phosphorylation is completely abolished in HBMECs lacking vimentin and PSF. Phosphorylation of ERK and nuclear translocation of NF-κB are entirely dependent on PSF. These findings suggest that vimentin and PSF cooperatively contribute to IbeA-induced cytoplasmic activation and nuclear translocation of NF-κB activation. PSF is essential for translocation of NF-κB and ERK to the nucleus. These findings reveal previously unappreciated facets of the IbeA-binding proteins. Cooperative contributions of vimentin and PSF to IbeA-induced cytoplasmic activation and nuclear translocation of NF-κB may represent a new paradigm in pathogen-induced signal transduction and lead to the development of novel strategies for the prevention and treatment of bacterial meningitis.
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影响因子：
--
作者：
Chi F;Wang Y;Gallaher TK;Wu CH;Jong A;Huang SH
通讯作者：
Huang SH
DOI：
10.1073/pnas.78.12.7550
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BENNETT, V;DAVIS, J
通讯作者：
DAVIS, J
影响因子：
4.8
作者：
Dong, XS;Shylnova, O;Lye, SJ
通讯作者：
Lye, SJ
影响因子：
3.1
作者：
HUANG, SH;WASS, C;KIM, KS
通讯作者：
KIM, KS
影响因子：
4.8
作者：
Higuero, Alonso M.;Sanchez-Ruiloba, Lucia;Iglesias, Teresa
通讯作者：
Iglesias, Teresa