Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands
Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands
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DOI：
10.1152/ajplung.00053.2013
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发表时间：
2013-12-01
影响因子：
4.9
通讯作者：
Ichinose, Masakazu
中科院分区：
文献类型：
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作者：
Muramatsu, Soshi;Tamada, Tsutomu;Ichinose, Masakazu
Muramatsu S、Tamada T、Nara M、Murakami K、Kikuchi T、Kanehira M、Maruyama Y、Ebina M、Nukiwa T、Ichinose M。鞭毛蛋白/TLR5 信号增强猪气管粘膜下腺的气道浆液分泌。 Am J Physiol Lung Cell Mol Physiol 305：L819-L830，2013。首次发表于 2013 年 10 月 4 日； doi:10.1152/ajplung.00053.2013.-气道浆液分泌对于维持气道粘膜中的粘液纤毛运输至关重要，这负责粘膜免疫的上调。尽管有很多文章讨论 Toll 样受体 (TLR) 在气道免疫系统中的重要性，但 TLR 与气道浆液分泌之间的直接关系尚未得到很好的研究。在这里，我们重点关注铜绿假单胞菌的成分之一TLR5配体鞭毛蛋白是否参与气道浆液分泌的上调。制备新鲜分离的猪气管粘膜下腺细胞，并应用标准膜片钳技术测量这些细胞的全细胞离子响应。鞭毛蛋白对这些由生理相关的低剂量乙酰胆碱 (ACh) 诱导的振荡电流以剂量依赖性方式显示出增强作用。这些增强作用依赖于 TLR5，但不依赖于 TLR4。一氧化氮 (NO) 合酶抑制剂和 cGMP 依赖性蛋白激酶 (cGK) 抑制剂都消除了这些鞭毛蛋白诱导的增强作用。此外，TLR5在气管粘膜下腺上大量表达。鞭毛蛋白/TLR5 信号进一步加速了 ACh 诱导的细胞内 NO 合成。这些发现表明，TLR5 作为气道浆液分泌物的独特内源性增强剂参与气道粘膜防御系统，并且 NO/cGMP/cGK 信号传导参与了 TLR5 信号传导的这种快速增强作用。
Muramatsu S, Tamada T, Nara M, Murakami K, Kikuchi T, Kanehira M, Maruyama Y, Ebina M, Nukiwa T, Ichinose M. Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands. Am J Physiol Lung Cell Mol Physiol 305: L819-L830, 2013. First published October 4, 2013; doi:10.1152/ajplung.00053.2013.-Airway serous secretion is essential for the maintenance of mucociliary transport in airway mucosa, which is responsible for the upregulation of mucosal immunity. Although there are many articles concerning the importance of Toll-like receptors (TLRs) in airway immune systems, the direct relationship between TLRs and airway serous secretion has not been well investigated. Here, we focused on whether TLR5 ligand flagellin, which is one of the components of Pseudomonas aeruginosa, is involved in the upregulation of airway serous secretion. Freshly isolated swine tracheal submucosal gland cells were prepared, and the standard patch-clamp technique was applied for measurements of the whole cell ionic responses of these cells. Flagellin showed potentiating effects on these oscillatory currents induced by physiologically relevant low doses of acetylcholine (ACh) in a dose-dependent manner. These potentiating effects were TLR5 dependent but TLR4 independent. Both nitric oxide (NO) synthase inhibitors and cGMP-dependent protein kinase (cGK) inhibitors abolished these flagellin-induced potentiating effects. Furthermore, TLR5 was abundantly expressed on tracheal submucosal glands. Flagellin/TLR5 signaling further accelerated the intracellular NO synthesis induced by ACh. These findings suggest that TLR5 takes part in the airway mucosal defense systems as a unique endogenous potentiator of airway serous secretions and that NO/cGMP/cGK signaling is involved in this rapid potentiation by TLR5 signaling.