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Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell injury model.
Free Radic Biol Med. 2019 04; 134:229-238.FR

Abstract

Transient receptor potential protein (TRP) ion channels TRPA1 and TRPV1 may be important in mediating airway tissue injury and inflammation. This study was designed to clarify the role of TRPA1 and TRPV1 channels in cigarette smoke extract (CSE)-induced damage to bronchial and alveolar epithelial cells. Alveolar epithelial (A549) cells and bronchial epithelial (Beas-2B) cells were treated with CSE in the presence and absence of a TRPA1 inhibitor (100 μM, A967079), a TRPV1 inhibitor (100 μM, AMG9810) or both. DCFH-DA and MitoSOX Red probes were used to assay intracellular and mitochondrial oxidative stress, respectively. The mRNA levels of inflammatory mediators (IL-1β, IL-8, IL-18, IL-33) and antioxidants (HO-1, NQO1, MnSOD, catalase) and the protein expression levels of mitochondrial and inflammasome factors (MFN2, OPA1, DRP1, MFF, NLRP3,caspase-1) were respectively detected by RT-PCR and Western Blot. The results were validated in TRPA1 shRNA and TRPV1 shRNA cells. In both cell types, 10% CSE increased intracellular and mitochondrial oxidative stress, induced Ca2+ influx, increased inflammatory gene expression, reduced antioxidant gene expression and inhibited the activities of mitochondrial respiratory chain (MRC) complexes. 10% CSE increased the expression of mitochondrial fission proteins (MFF and DRP1), Caspase-1 and NLRP3 protein expression and decreased that of mitochondrial fusion proteins (MFN2 and OPA1). Both inhibitors and gene-knockout of TRPA1 and TRPV1 reduced oxidative stress, blocked Ca2+ influx, and inhibited inflammatory and increased antioxidant gene expression. They also prevented the changes in mitochondrial fission and fusion proteins and in MRC complexes activities induced by CSE. Both TRPA1 and TRPV1 mediate CSE-induced damage of bronchial and alveolar epithelial cells via modulation of oxidative stress, inflammation and mitochondrial damage and their inhibition should be considered as potential therapy for COPD.

Authors+Show Affiliations

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, NO.241, West HuaiHai Road, Shanghai 200030, PR China; Department of Respiratory and Critical Care, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, NO.218, Jixi Road, Hefei, Anhui, 230022, .PR China.Department of Respiratory and Critical Care, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, NO.218, Jixi Road, Hefei, Anhui, 230022, .PR China.Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, NO.241, West HuaiHai Road, Shanghai 200030, PR China; Department of Respiratory and Critical Care, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, NO.218, Jixi Road, Hefei, Anhui, 230022, .PR China.Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, NO.241, West HuaiHai Road, Shanghai 200030, PR China.Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, NO.241, West HuaiHai Road, Shanghai 200030, PR China.Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, NO.241, West HuaiHai Road, Shanghai 200030, PR China. Electronic address: lifeng741@aliyun.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30639616

Citation

Wang, Muyun, et al. "Roles of TRPA1 and TRPV1 in Cigarette Smoke -induced Airway Epithelial Cell Injury Model." Free Radical Biology & Medicine, vol. 134, 2019, pp. 229-238.
Wang M, Zhang Y, Xu M, et al. Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell injury model. Free Radic Biol Med. 2019;134:229-238.
Wang, M., Zhang, Y., Xu, M., Zhang, H., Chen, Y., Chung, K. F., Adcock, I. M., & Li, F. (2019). Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell injury model. Free Radical Biology & Medicine, 134, 229-238. https://doi.org/10.1016/j.freeradbiomed.2019.01.004
Wang M, et al. Roles of TRPA1 and TRPV1 in Cigarette Smoke -induced Airway Epithelial Cell Injury Model. Free Radic Biol Med. 2019;134:229-238. PubMed PMID: 30639616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell injury model. AU - Wang,Muyun, AU - Zhang,Yanbei, AU - Xu,Mengmeng, AU - Zhang,Hai, AU - Chen,Yuqing, AU - Chung,Kian Fan, AU - Adcock,Ian M, AU - Li,Feng, Y1 - 2019/01/09/ PY - 2018/10/01/received PY - 2018/12/26/revised PY - 2019/01/03/accepted PY - 2019/1/15/pubmed PY - 2020/3/27/medline PY - 2019/1/15/entrez KW - Airway epithelial cell injury KW - COPD KW - Cigarette smoke KW - Mitochondria damage KW - Oxidative stress KW - TRPA1 KW - TRPV1 SP - 229 EP - 238 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 134 N2 - Transient receptor potential protein (TRP) ion channels TRPA1 and TRPV1 may be important in mediating airway tissue injury and inflammation. This study was designed to clarify the role of TRPA1 and TRPV1 channels in cigarette smoke extract (CSE)-induced damage to bronchial and alveolar epithelial cells. Alveolar epithelial (A549) cells and bronchial epithelial (Beas-2B) cells were treated with CSE in the presence and absence of a TRPA1 inhibitor (100 μM, A967079), a TRPV1 inhibitor (100 μM, AMG9810) or both. DCFH-DA and MitoSOX Red probes were used to assay intracellular and mitochondrial oxidative stress, respectively. The mRNA levels of inflammatory mediators (IL-1β, IL-8, IL-18, IL-33) and antioxidants (HO-1, NQO1, MnSOD, catalase) and the protein expression levels of mitochondrial and inflammasome factors (MFN2, OPA1, DRP1, MFF, NLRP3,caspase-1) were respectively detected by RT-PCR and Western Blot. The results were validated in TRPA1 shRNA and TRPV1 shRNA cells. In both cell types, 10% CSE increased intracellular and mitochondrial oxidative stress, induced Ca2+ influx, increased inflammatory gene expression, reduced antioxidant gene expression and inhibited the activities of mitochondrial respiratory chain (MRC) complexes. 10% CSE increased the expression of mitochondrial fission proteins (MFF and DRP1), Caspase-1 and NLRP3 protein expression and decreased that of mitochondrial fusion proteins (MFN2 and OPA1). Both inhibitors and gene-knockout of TRPA1 and TRPV1 reduced oxidative stress, blocked Ca2+ influx, and inhibited inflammatory and increased antioxidant gene expression. They also prevented the changes in mitochondrial fission and fusion proteins and in MRC complexes activities induced by CSE. Both TRPA1 and TRPV1 mediate CSE-induced damage of bronchial and alveolar epithelial cells via modulation of oxidative stress, inflammation and mitochondrial damage and their inhibition should be considered as potential therapy for COPD. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/30639616/Roles_of_TRPA1_and_TRPV1_in_cigarette_smoke__induced_airway_epithelial_cell_injury_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(18)31748-9 DB - PRIME DP - Unbound Medicine ER -