Background: Transient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) mediate
the development of lung injury and inflammation. This study investigated the role and mechanism of the
TRPA1/TRPV1 pathway in airway inflammation and bronchial hyperresponsiveness (BHR) induced by
acute ozone exposure.
Methods: C57BL/6 mice (8–10 weeks) were intraperitoneally injected with phosphate buffered saline
(PBS), A967079 (TRPA1 inhibitor) or AMG9810 (TRPV1 inhibitor) 1 h before or after ozone exposure
(2.5 ppm, 3 h). BHR, cell counts in bronchoalveolar lavage (BAL) fluid, oxidative stress biomarkers,
inflammatory cytokines, TRPA1 and TPRV1 protein levels, mitochondrial dynamics- and mitophagy-related
protein levels, and activities of mitochondrial respiratory chain (MRC) in lung were measured.
Results: The preventive treatment effect was similar to the therapeutic treatment effect. Both A967079 and
AMG9810 intervention suppressed BHR, inflammatory cytokines, total BAL fluid cells, malondialdehyde
(MDA) levels and inflammatory cytokines mRNA including Substance P (SP), Keratinocyte-Derived
Chemokine (KC), interleukin18 (IL-18) and chemokine (C-X-C motif) ligand 8 (CXCL8) expression, and
enhanced reduced glutathione (GSH)/oxidized glutathione (GSSG) levels compared with ozone-exposed
mice. A967079 and AMG9810 intervention inhibited dynamin-related protein (DRP1), mitochondrial fission
factor (MFF), Parkinson protein 2 E3 ubiquitin protein ligase (PARK2) and Sequestosome 1 (SQSTM1)/p62
expression, increased Optic atrophy 1 (OPA1), mitofusin 2 (MFN2) and PTEN-induced putative kinase 1
(PINK1) expression, and up-regulated the activities of MRC complex III and V in lung tissue.
Conclusions: The results show that both TRPA1 and TRPV1 pathways are involved in acute ozone
exposure-induced airway inflammation and BHR and influence oxidative stress, mitochondrial quality
control and MRC activity, which could be a potential target for clinical therapy of respiritory disease