TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells.
TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells.
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DOI：
10.1038/s41467-017-01201-3
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发表时间：
2017-10-20
影响因子：
16.6
通讯作者：
Talavera K
中科院分区：
文献类型：
--
作者：
Alpizar YA;Boonen B;Sanchez A;Jung C;López-Requena A;Naert R;Steelant B;Luyts K;Plata C;De Vooght V;Vanoirbeek JAJ;Meseguer VM;Voets T;Alvarez JL;Hellings PW;Hoet PHM;Nemery B;Valverde MA;Talavera K
脂多糖（LPS），革兰氏阴性菌壁的主要成分，通过被认为仅依赖于Toll样受体4（TLR4）免疫途径的机制在气道中触发强大的防御反应。在这里，我们表明，气道上皮细胞显示增加细胞内Ca2+浓度在LPS应用的几秒钟内。这种反应通过激活瞬时受体电位香草酸4阳离子通道（TRPV4）以TLR4非依赖性方式发生。我们发现TRPV4介导了LPS诱导的纤毛搏动频率的增加和杀菌性一氧化氮的产生。在LPS攻击后，TRPV4缺陷小鼠显示出加重的炎症变化和多形核白细胞向气道中的募集。我们的结论是，LPS诱导的TRPV4激活触发信号传导机制，其操作速度更快，独立于典型的TLR4免疫途径，导致立即的保护性反应，如直接的抗菌作用，增加气道清除，以及炎症性先天免疫反应的调节。LPS是革兰氏阴性细菌细胞壁的主要成分，并通过激活TLR4触发气道上皮的免疫应答。在这里，作者表明LPS也激活TRPV4，从而诱导快速防御反应，如一氧化氮的产生和小鼠纤毛跳动的增加。
Lipopolysaccharides (LPS), the major components of the wall of gram-negative bacteria, trigger powerful defensive responses in the airways via mechanisms thought to rely solely on the Toll-like receptor 4 (TLR4) immune pathway. Here we show that airway epithelial cells display an increase in intracellular Ca2+ concentration within seconds of LPS application. This response occurs in a TLR4-independent manner, via activation of the transient receptor potential vanilloid 4 cation channel (TRPV4). We found that TRPV4 mediates immediate LPS-induced increases in ciliary beat frequency and the production of bactericidal nitric oxide. Upon LPS challenge TRPV4-deficient mice display exacerbated ventilatory changes and recruitment of polymorphonuclear leukocytes into the airways. We conclude that LPS-induced activation of TRPV4 triggers signaling mechanisms that operate faster and independently from the canonical TLR4 immune pathway, leading to immediate protective responses such as direct antimicrobial action, increase in airway clearance, and the regulation of the inflammatory innate immune reaction. LPS is a major component of gram-negative bacterial cell walls, and triggers immune responses in airway epithelium by activating TLR4. Here the authors show that LPS also activates TRPV4, thereby inducing fast defense responses such as nitric oxide production and increased ciliary beating in mice.
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影响因子：
3.9
作者：
Jackson, Claire L.;Lucas, Jane S.;Lackie, Peter M.
通讯作者：
Lackie, Peter M.
DOI：
10.1152/ajplung.00315.2009
发表时间：
2010-09-01
影响因子：
4.9
作者：
Hamanaka, Kazutoshi;Jian, Ming-Yuan;Parker, James C.
通讯作者：
Parker, James C.
影响因子：
7.6
作者：
Diogenes, A.;Ferraz, C. C. R.;Hargreaves, K. M.
通讯作者：
Hargreaves, K. M.
影响因子：
15.9
作者：
Bessac, Bret F.;Sivula, Michael;Jordt, Sven-Eric
通讯作者：
Jordt, Sven-Eric
DOI：
10.1083/jcb.200409070
发表时间：
2005-03-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Andrade YN;Fernandes J;Vázquez E;Fernández-Fernández JM;Arniges M;Sánchez TM;Villalón M;Valverde MA
通讯作者：
Valverde MA