Activation of
TRPV3 by Wood Smoke Particles and Roles
in Pneumotoxicity
Version 4 2019-04-16, 08:13
Version 3 2019-01-18, 22:44
Version 2 2018-04-30, 18:57
Version 1 2018-04-30, 18:50
Posted on 2019-04-16 - 08:13
Wood/biomass
smoke particulate materials (WBSPM) are pneumotoxic,
but the mechanisms by which these materials affect lung cells are
not fully understood. We previously identified transient receptor
potential (TRP) ankyrin-1 as a sensor for electrophiles in WBSPM and
hypothesized that other TRP channels expressed by lung cells might
also be activated by WBSPM, contributing to pneumotoxicity.
Screening TRP channel activation by WBSPM using calcium flux assays
revealed TRPV3 activation by materials obtained from burning multiple
types of wood under fixed conditions. TRPV3 activation by WBSPM was
dependent on the chemical composition, and the pattern of activation
and chemical components of PM agonists was different from that of
TRPA1. Chemical analysis of particle constituents by gas chromatography–mass
spectrometry and principal component analysis indicated enrichment
of cresol, ethylphenol, and xylenol analogues, plus several
other chemicals among the most potent samples. 2,3-, 2,4-, 2,5-, 2,6-,
3,4-, and 3,5-xylenol, 2-, 3-, and 4-ethylphenol, 2-methoxy-4-methylphenol,
and 5,8-dihydronaphthol were TRPV3 agonists exhibiting preferential
activation versus TRPA1, M8, V1, and V4. The concentration of 2,3-
and 3,4-xylenol in the most potent samples of pine and mesquite smoke
PM (<3 μm) was 0.1–0.3% by weight, while that of 5,8-dihydronaphthol
was 0.03%. TRPV3 was expressed by several human lung epithelial cell
lines, and both pine PM and pure chemical TRPV3 agonists found in
WBSPM were more toxic to TRPV3-over-expressing cells via TRPV3 activation.
Finally, mice treated sub-acutely with pine particles exhibited an
increase in sensitivity to inhaled methacholine involving TRPV3. In
summary, TRPV3 is activated by specific chemicals in WBSPM, potentially
contributing to the pneumotoxic properties of certain WBSPM.
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Deering-Rice, Cassandra
E.; Nguyen, Nam; Lu, Zhenyu; Cox, James E.; Shapiro, Darien; Romero, Erin G.; et al. (2018). Activation of
TRPV3 by Wood Smoke Particles and Roles
in Pneumotoxicity. ACS Publications. Collection. https://doi.org/10.1021/acs.chemrestox.7b00336
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AUTHORS (10)
CD
Cassandra
E. Deering-Rice
NN
Nam Nguyen
ZL
Zhenyu Lu
JC
James E. Cox
DS
Darien Shapiro
ER
Erin G. Romero
VM
Virginia K. Mitchell
KB
Katherine L. Burrell
JV
John M. Veranth
CR
Christopher A. Reilly