Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-α, and IL-1β
Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-α, and IL-1β
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DOI：
10.1152/ajpcell.00166.2005
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发表时间：
2006-03-01
影响因子：
5.5
通讯作者：
Machen, TE
中科院分区：
文献类型：
--
作者：
Tseng, J;Do, J;Machen, TE
我们测量了先天性免疫反应的原代人气管上皮（HTE）细胞生长融合，假分层层暴露于顶面与基底面的炎症激活剂。顶端铜绿假单胞菌菌株PAK（但不是鞭毛蛋白突变体PAK中心点fliC）、鞭毛蛋白和鞭毛蛋白+ PAK中心点fliC激活NF-B-κ和IL-8表达和分泌。相反，与鞭毛蛋白相比，HTE细胞对LPS不敏感。鞭毛蛋白在柱状细胞中激活NF-B-κ，但在基底细胞中不激活。IL-1 β + TNF-α引起的反应类似于鞭毛蛋白。基底外侧鞭毛蛋白或IL-1 β + TNF-α引起1.5至4倍的反应，这与NF-B-κ活化发生在柱状细胞和基底细胞中的事实一致。MyD 88（toll受体相关衔接子）、IL-1受体（IL 1 R）1和TNF-α受体（TNFR）1在柱状细胞和基底细胞中表达。ZO-1主要定位于柱状细胞的紧密连接处，而不定位于基底细胞。我们推断如下。1)在铜绿假单胞菌在气道表面液体（ASL）中积聚期间，鞭毛蛋白是触发柱状细胞中的炎症反应所必需且足够的;柱状细胞表达toll样受体5和MyD 88，通常与鞭毛蛋白激活的细胞信号传导相关。2)ASL中的IL-1 β + TNF-alpha也激活柱状细胞，并且这些细胞也表达IL 1 R1和TNFR 1。3)顶端鞭毛蛋白、IL-1 β和TNF-α不激活基底细胞，因为柱状细胞之间的紧密连接阻止从顶端表面进入基底细胞。4)基底外侧表面暴露于炎性激活剂引起更大的反应，因为柱状细胞和基底细胞都被激活，可能是因为两种细胞类型都表达鞭毛蛋白、IL-1 β和TNF-α的受体。
We measured innate immune responses by primary human tracheal epithelial (HTE) cells grown as confluent, pseudostratified layers during exposure to inflammatory activators on apical vs. basolateral surfaces. Apical Pseudomonas aeruginosa strain PAK ( but not flagellin mutant PAK center dot fliC), flagellin, and flagellin + PAK center dot fliC activated NF-B-kappa and IL-8 expression and secretion. In contrast, HTE cells were insensitive to LPS compared to flagellin. Flagellin activated NF-B-kappa in columnar but not basal cells. IL-1 beta + TNF-alpha elicited responses similar to those of flagellin. Basolateral flagellin or IL-1 beta + TNF-alpha caused 1.5- to 4-fold larger responses, consistent with the fact that NF-B-kappa activation occurred in both columnar and basal cells. MyD88 (toll receptor-associated adapter), IL-1 receptor (IL1R)1, and TNF-alpha receptor (TNFR)1 were expressed in columnar and basal cells. ZO-1 was localized to tight junctions of columnar cells but not to basal cells. We infer the following. 1) Flagellin is necessary and sufficient to trigger inflammatory responses in columnar cells during accumulation of P. aeruginosa in the airway surface liquid (ASL); columnar cells express toll-like receptor 5 and MyD88, often associated with flagellin-activated cell signaling. 2) IL-1 beta + TNF-alpha in the ASL also activate columnar cells, and these cells also express IL1R1 and TNFR1. 3) Apical flagellin, IL-1 beta, and TNF-alpha do not activate basal cells because tight junctions between columnar cells prevent access from the apical surface to the basal cells. 4) Exposure of basolateral surfaces to inflammatory activators elicits larger responses because both columnar and basal cells are activated, likely because both cell types express receptors for flagellin, IL-1 beta, and TNF-alpha.