Channelpedia

PubMed 21245013


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPV , TRPV4



Title: TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles.

Authors: Jinju Li, Patrick Kanju, Michael Patterson, Wei-Leong Chew, Seung-Hyun Cho, Ian Gilmour, Tim Oliver, Ryohei Yasuda, Andrew Ghio, Sidney A Simon, Wolfgang Liedtke

Journal, date & volume: Environ. Health Perspect., 2011 Jun , 119, 784-93

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21245013


Abstract
Human respiratory epithelia function in airway mucociliary clearance and barrier function and have recently been implicated in sensory functions.We investigated a link between chronic obstructive pulmonary disease (COPD) pathogenesis and molecular mechanisms underlying Ca2+ influx into human airway epithelia elicited by diesel exhaust particles (DEP).Using primary cultures of human respiratory epithelial (HRE) cells, we determined that these cells possess proteolytic signaling machinery, whereby proteinase-activated receptor-2 (PAR-2) activates Ca2+-permeable TRPV4, which leads to activation of human respiratory disease-enhancing matrix metalloproteinase-1 (MMP-1), a signaling cascade initiated by diesel exhaust particles (DEP), a globally relevant air pollutant. Moreover, we observed ciliary expression of PAR-2, TRPV4, and phospholipase-Cβ3 in human airway epithelia and their DEP-enhanced protein-protein complex formation. We also found that the chronic obstructive pulmonary disease (COPD)-predisposing TRPV4P19S variant enhances Ca2+ influx and MMP 1 activation, providing mechanistic linkage between man-made air pollution and human airway disease.DEP evoked protracted Ca2+ influx via TRPV4, enhanced by the COPD-predisposing human genetic polymorphism TRPV4P19S. This mechanism reprograms maladaptive inflammatory and extracellular-matrix-remodeling responses in human airways. The novel concept of air pollution-responsive ciliary signal transduction from PAR-2 to TRPV4 in human respiratory epithelia will accelerate rationally targeted therapies, possibly via the inhalatory route.