Role of TRPA1/TRPV1 in acute ozone exposure induced murine model of airway inflammation and bronchial hyperresponsiveness
| Autor: | Chenfei Li, Hai Zhang, Liangyu Wei, Qi Liu, Meiqin Xie, Jiali Weng, Xiaohui Wang, Kian Fan Chung, Ian M. Adcock, Yuqing Chen, Feng Li |
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| Rok vydání: | 2022 |
| Předmět: |
Cervical esophageal cancer (CEC)
Pulmonary and Respiratory Medicine MITOCHONDRIAL FISSION Respiratory System TRP CHANNELS CHEMORADIOTHERAPY MECHANISMS neoadjuvant chemoradiotherapy stratified treatment TRP vanilloid 1 (TRPV1) Bronchial hyperresponsiveness (BHR) oxidative stress PRESERVATION Science & Technology transient receptor potential (TRP) ankyrin 1 (TRPA1)/TRP vanilloid 1 (TRPV1) 1103 Clinical Sciences chemoradiation therapy (dCRT) SUBSTANCE-P CANCER mitochondria damage ozone transient receptor potential (TRP) ankyrin 1 (TRPA1) definitive SURGICAL-MANAGEMENT immunotherapy Life Sciences & Biomedicine |
| Zdroj: | Journal of Thoracic Disease. 14:2698-2711 |
| ISSN: | 2077-6624 2072-1439 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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