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

Yeranddy A. Alpizar, Brett Boonen, Alicia Sanchez, Carole Jung, Alejandro López-Requena, Robbe Naert, Brecht Steelant, Katrien Luyts, Cristina Plata, Vanessa De Vooght, Jeroen A. J. Vanoirbeek, Victor M. Meseguer, Thomas Voets, Julio L. Alvarez, Peter W. Hellings, Peter H. M. Hoet, Benoit Nemery, Miguel A. Valverde and Karel Talavera ()
Additional contact information
Yeranddy A. Alpizar: Laboratory for Ion Channel Research, KU Leuven
Brett Boonen: Laboratory for Ion Channel Research, KU Leuven
Alicia Sanchez: Laboratory for Ion Channel Research, KU Leuven
Carole Jung: Laboratory of Molecular Physiology and Channelopathies, Universitat Pompeu Fabra
Alejandro López-Requena: Laboratory for Ion Channel Research, KU Leuven
Robbe Naert: Laboratory for Ion Channel Research, KU Leuven
Brecht Steelant: Laboratory of Clinical Immunology, KU Leuven
Katrien Luyts: Laboratory of Environment and Health, KU Leuven
Cristina Plata: Laboratory of Molecular Physiology and Channelopathies, Universitat Pompeu Fabra
Vanessa De Vooght: Laboratory of Environment and Health, KU Leuven
Jeroen A. J. Vanoirbeek: Laboratory of Environment and Health, KU Leuven
Victor M. Meseguer: Universidad Miguel Hernández-CSIC
Thomas Voets: Laboratory for Ion Channel Research, KU Leuven
Julio L. Alvarez: Laboratory for Ion Channel Research, KU Leuven
Peter W. Hellings: Laboratory of Clinical Immunology, KU Leuven
Peter H. M. Hoet: Laboratory of Environment and Health, KU Leuven
Benoit Nemery: Laboratory of Environment and Health, KU Leuven
Miguel A. Valverde: Laboratory of Molecular Physiology and Channelopathies, Universitat Pompeu Fabra
Karel Talavera: Laboratory for Ion Channel Research, KU Leuven

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01201-3

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