In this section
@article{Wang:2019:10.1016/j.freeradbiomed.2019.01.004,
author = {Wang, M and Zhang, Y and Xu, M and Zhang, H and Chen, Y and Chung, KF and Adcock, IM and Li, F},
doi = {10.1016/j.freeradbiomed.2019.01.004},
journal = {Free Radical Biology and Medicine},
pages = {229--238},
title = {Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell injury model},
url = {http://dx.doi.org/10.1016/j.freeradbiomed.2019.01.004},
volume = {134},
year = {2019}
}
TY - JOUR
AB - 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 (100μM, A967079), a TRPV1 inhibitor (100μM, 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.
AU - Wang,M
AU - Zhang,Y
AU - Xu,M
AU - Zhang,H
AU - Chen,Y
AU - Chung,KF
AU - Adcock,IM
AU - Li,F
DO - 10.1016/j.freeradbiomed.2019.01.004
EP - 238
PY - 2019///
SN - 0891-5849
SP - 229
TI - Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell injury model
T2 - Free Radical Biology and Medicine
UR - http://dx.doi.org/10.1016/j.freeradbiomed.2019.01.004
UR - https://www.ncbi.nlm.nih.gov/pubmed/30639616
UR - http://hdl.handle.net/10044/1/68474
VL - 134
ER -