Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity

Area of Science:

• Toxicology
• Molecular Biology
• Environmental Health

Background:

• Wood/biomass smoke particulate materials (WBSPM) are known to be pneumotoxic.
• The precise mechanisms of WBSPM-induced lung cell damage are not fully understood.
• Transient receptor potential ankyrin-1 (TRPA1) was previously identified as a WBSPM sensor.

Purpose of the Study:

• To investigate the role of other transient receptor potential (TRP) channels in WBSPM-induced pneumotoxicity.
• To identify specific WBSPM components that activate TRP channels in lung cells.
• To determine the contribution of TRPV3 activation to WBSPM toxicity.

Main Methods:

• Calcium flux assays to screen TRP channel activation by WBSPM.
• Gas chromatography-mass spectrometry and principal component analysis for chemical characterization of WBSPM.
• In vitro studies using human lung epithelial cell lines.
• In vivo studies in mice.

Main Results:

• TRPV3 channels were activated by WBSPM from various wood types.
• Activation patterns and chemical agonists differed between TRPV3 and TRPA1.
• Xylenol, ethylphenol, and dihydronaphthol analogues were identified as potent TRPV3 agonists in WBSPM.
• WBSPM and its chemical agonists were more toxic to TRPV3-over-expressing lung cells.
• Mice exposed to pine WBSPM showed increased methacholine sensitivity mediated by TRPV3.

Conclusions:

• TRPV3 is a significant sensor for specific chemical components in WBSPM.
• TRPV3 activation by WBSPM contributes to its pneumotoxic effects.
• Understanding TRPV3's role may inform strategies to mitigate WBSPM-related respiratory harm.