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

Publication ,  Journal Article
Li, J; Kanju, P; Patterson, M; Chew, W-L; Cho, S-H; Gilmour, I; Oliver, T; Yasuda, R; Ghio, A; Simon, SA; Liedtke, W
Published in: Environ Health Perspect
June 2011

BACKGROUND: Human respiratory epithelia function in airway mucociliary clearance and barrier function and have recently been implicated in sensory functions. OBJECTIVE: 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). METHODS AND RESULTS: 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. CONCLUSION: 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.

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Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

June 2011

Volume

119

Issue

6

Start / End Page

784 / 793

Location

United States

Related Subject Headings

  • Vehicle Emissions
  • Toxicology
  • TRPV Cation Channels
  • Signal Transduction
  • Respiratory Mucosa
  • Receptor, PAR-2
  • Pulmonary Disease, Chronic Obstructive
  • Phospholipase C beta
  • Particulate Matter
  • Matrix Metalloproteinase 1
 

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Li, J., Kanju, P., Patterson, M., Chew, W.-L., Cho, S.-H., Gilmour, I., … Liedtke, W. (2011). TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles. Environ Health Perspect, 119(6), 784–793. https://doi.org/10.1289/ehp.1002807
Li, Jinju, Patrick Kanju, Michael Patterson, Wei-Leong Chew, Seung-Hyun Cho, Ian Gilmour, Tim Oliver, et al. “TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles.Environ Health Perspect 119, no. 6 (June 2011): 784–93. https://doi.org/10.1289/ehp.1002807.
Li J, Kanju P, Patterson M, Chew W-L, Cho S-H, Gilmour I, et al. TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles. Environ Health Perspect. 2011 Jun;119(6):784–93.
Li, Jinju, et al. “TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles.Environ Health Perspect, vol. 119, no. 6, June 2011, pp. 784–93. Pubmed, doi:10.1289/ehp.1002807.
Li J, Kanju P, Patterson M, Chew W-L, Cho S-H, Gilmour I, Oliver T, Yasuda R, Ghio A, Simon SA, Liedtke W. TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles. Environ Health Perspect. 2011 Jun;119(6):784–793.

Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

June 2011

Volume

119

Issue

6

Start / End Page

784 / 793

Location

United States

Related Subject Headings

  • Vehicle Emissions
  • Toxicology
  • TRPV Cation Channels
  • Signal Transduction
  • Respiratory Mucosa
  • Receptor, PAR-2
  • Pulmonary Disease, Chronic Obstructive
  • Phospholipase C beta
  • Particulate Matter
  • Matrix Metalloproteinase 1