TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells

被引:94
作者
Alpizar, Yeranddy A. [1 ,2 ]
Boonen, Brett [1 ,2 ]
Sanchez, Alicia [1 ,2 ]
Jung, Carole [3 ]
Lopez-Requena, Alejandro [1 ,2 ]
Naert, Robbe [1 ,2 ]
Steelant, Brecht [4 ]
Luyts, Katrien [5 ]
Plata, Cristina [3 ]
De Vooght, Vanessa [5 ]
Vanoirbeek, Jeroen A. J. [5 ]
Meseguer, Victor M. [6 ]
Voets, Thomas [1 ,2 ]
Alvarez, Julio L. [1 ]
Hellings, Peter W. [4 ,7 ]
Hoet, Peter H. M. [5 ]
Nemery, Benoit [5 ]
Valverde, Miguel A. [3 ]
Talavera, Karel [1 ,2 ]
机构
[1] Katholieke Univ Leuven, Dept Cellular & Mol Med, Lab Ion Channel Res, B-3000 Leuven, Belgium
[2] VIB Ctr Brain & Dis Res, B-3000 Leuven, Belgium
[3] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Lab Mol Physiol & Channelopathies, Barcelona 08003, Spain
[4] Katholieke Univ Leuven, Dept Microbiol & Immunol, Lab Clin Immunol, B-3000 Leuven, Belgium
[5] Katholieke Univ Leuven, Dept Publ Hlth & Care, Lab Environm & Hlth, B-3000 Leuven, Belgium
[6] Univ Miguel Hernandez, Inst Neurociencias Alicante, CSIC, E-03550 Alacant, Spain
[7] Univ Ghent, Dept Otorhinolaryngol, Upper Airways Res Lab, B-9000 Ghent, Belgium
关键词
INDUCIBLE NITRIC-OXIDE; SYNTHASE EXPRESSION; LUNG INJURY; ENDOTOXIN; CHANNEL; INFLAMMATION; ADHESION; DUST; TLR4; SEQUESTRATION;
D O I
10.1038/s41467-017-01201-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:13
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