TRPV4 Protects the Lung from Bacterial Pneumonia via MAPK Molecular Pathway Switching.

ABSTRACT: Mechanical cell-matrix interactions can drive the innate immune responses to infection; however, the molecular underpinnings of these responses remain elusive. This study was undertaken to understand the molecular mechanism by which the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4), alters the in vivo response to lung infection. For the first time, to our knowledge, we show that TRPV4 protects the lung from injury upon intratracheal Pseudomonas aeruginosa in mice. TRPV4 functions to enhance macrophage bacterial clearance and downregulate proinflammatory cytokine secretion. TRPV4 mediates these effects through a novel mechanism of molecular switching of LPS signaling from predominant activation of the MAPK, JNK, to that of p38. This is accomplished

SUBMITTER: Scheraga RG 

PROVIDER: S-EPMC7033031 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature