Original Article
Rosiglitazone inhibits PM2.5-induced cytotoxicity in human lung epithelial A549 cells
Abstract
Background: Exposure to fine particulate matter <2.5 µm in diameter (PM2.5) leads to global adverse health effects, including increases in morbidity and mortality of respiratory diseases. PM2.5 increases production of reactive oxygen species (ROS) in the lung, which further lead to oxidative stress, cell apoptosis and cell death. According to results of previous studies, oxidative stress and subsequent cell apoptosis can be reduced by peroxisome proliferator-activated receptor gamma (PPARγ) in various cell types, however, its role in oxidative stress-related cell apoptosis caused by PM2.5 in respiratory systems is unclear.
Methods: Human lung alveolar epithelial A549 cells were exposed to PM2.5 with or without rosiglitazone (an agonist of PPARγ) treatment. Cellular apoptosis and intracellular oxidative stress were determined by flow cytometry based on FITC Annexin V and DCFH-DA fluorescence, respectively. Western blot was conducted to determine the expression of Bax, Bcl2, PPARγ, P-ERK1/2, ERK1/2, P-STAT3, and STAT3.
Results: PPARγ was downregulated in PM2.5-treated A549 cells, and application of rosiglitazone reduced PM2.5-mediated ROS generation and cell apoptosis. In addition, our results indicated that rosiglitazone treatment suppressed PM2.5-induced ERK1/2 and STAT3 activation.
Conclusions: Collectively, these data suggested that rosiglitazone protects against PM2.5-induced ROS production and cell apoptosis and represses activation of ERK1/2 and STAT3 signaling in A549 cells. Our results indicated that rosiglitazone is a potential therapeutic agent for PM2.5-induced lung diseases.
Methods: Human lung alveolar epithelial A549 cells were exposed to PM2.5 with or without rosiglitazone (an agonist of PPARγ) treatment. Cellular apoptosis and intracellular oxidative stress were determined by flow cytometry based on FITC Annexin V and DCFH-DA fluorescence, respectively. Western blot was conducted to determine the expression of Bax, Bcl2, PPARγ, P-ERK1/2, ERK1/2, P-STAT3, and STAT3.
Results: PPARγ was downregulated in PM2.5-treated A549 cells, and application of rosiglitazone reduced PM2.5-mediated ROS generation and cell apoptosis. In addition, our results indicated that rosiglitazone treatment suppressed PM2.5-induced ERK1/2 and STAT3 activation.
Conclusions: Collectively, these data suggested that rosiglitazone protects against PM2.5-induced ROS production and cell apoptosis and represses activation of ERK1/2 and STAT3 signaling in A549 cells. Our results indicated that rosiglitazone is a potential therapeutic agent for PM2.5-induced lung diseases.
