Modulation of the NF-kappaB pathway by Bordetella pertussis filamentous hemagglutinin.
Modulation of the NF-kappaB pathway by Bordetella pertussis filamentous hemagglutinin.
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Bordetella budtussis丝状血凝素对NF-kappab途径的调节。
DOI：
10.1371/journal.pone.0003825
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Relman DA
中科院分区：
文献类型：
--
作者：
Abramson T;Kedem H;Relman DA
丝状血凝素 (FHA) 是一种由百日咳博德特氏菌产生的细胞相关和分泌的粘附素，在宿主细胞中具有促凋亡和促炎症活性。鉴于 NF-κB 转录因子家族在这些宿主细胞反应中的重要性，我们研究了 FHA 对巨噬细胞和支气管上皮细胞中 NF-κB 激活的影响，这两种细胞都是自然感染期间的相关细胞类型。暴露于原代人单核细胞和转化的 U-937 巨噬细胞（而非 BEAS-2B 上皮细胞）的 FHA 会导致 NF-κB 通路的早期激活，表现为胞质 IκBα 的降解、NF-κB DNA 结合以及随后 NF-κB 调节的炎症细胞因子的分泌。然而，巨噬细胞和人单核细胞暴露于 FHA 两个小时或更长时间会导致胞质 IκBα 积累，并且 TNF-α 无法激活 NF-κB。将细胞暴露于 FHA 2 小时后，蛋白酶体活性减弱，BEAS-2B 细胞中 RelA 的核易位也是如此。这些结果揭示了复杂的时间动态，并表明尽管短期效果相反，但宿主细胞长时间暴露于这种分泌的粘附素可能会阻止 NF-κB 激活，并可能导致针对这种细菌病原体的免疫反应受损。
Filamentous hemagglutinin (FHA) is a cell-associated and secreted adhesin produced by Bordetella pertussis with pro-apoptotic and pro-inflammatory activity in host cells. Given the importance of the NF-κB transcription factor family in these host cell responses, we examined the effect of FHA on NF-κB activation in macrophages and bronchial epithelial cells, both of which are relevant cell types during natural infection. Exposure to FHA of primary human monocytes and transformed U-937 macrophages, but not BEAS-2B epithelial cells, resulted in early activation of the NF-κB pathway, as manifested by the degradation of cytosolic IκBα, by NF-κB DNA binding, and by the subsequent secretion of NF-κB-regulated inflammatory cytokines. However, exposure of macrophages and human monocytes to FHA for two hours or more resulted in the accumulation of cytosolic IκBα, and the failure of TNF-α to activate NF-κB. Proteasome activity was attenuated following exposure of cells to FHA for 2 hours, as was the nuclear translocation of RelA in BEAS-2B cells. These results reveal a complex temporal dynamic, and suggest that despite short term effects to the contrary, longer exposures of host cells to this secreted adhesin may block NF-κB activation, and perhaps lead to a compromised immune response to this bacterial pathogen.
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