Peroxisome Proliferator-Activated Receptor (PPARγ) Plays a Protective Role in Cigarette Smoking-Induced Inflammation via AMP-Activated Protein Kinase (AMPK) Signaling

BACKGROUND Cigarette smoking is a well-known risk factor in multiple chronic pulmonary diseases. This study aims to investigate the role of Peroxisome Proliferator-activated Receptor (PPAR) g in cigarette smoking-induced inflammation. MATERIAL AND METHODS Cigarette smoking extract (CSE) was employed to induce inflammation in bronchial epithelial cells (BECs). After CSE administration, several autophagy-related proteins (Beclin1, autophagy-related gene (ATG)5, ATG7, p62, and LC3) and PPARg levels were examined by western blot. Subsequently, PPARg agonists and antagonist were used to treat CSE-induced BECs, several inflammatory factors (interleukin (IL)-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2) and autophagy-related proteins were detected to measure the inflammatory and Autophagy levels. Then LC3 knockdown was performed to verify the role of Autophagy in CSE-induced inflammation. Finally, the AMP-activated protein kinase (AMPK) and its downstream S6 kinase (S6K) were detected in CSE-stimulated BECs. RESULTS CSE administration caused insufficient Autophagy and the decrease of PPARγ in BECs. The PPARγ agonists ameliorate the CSE-induced inflammation and promote the Autophagy development, evidenced by the changes of inflammatory factors and autophagy-related proteins. Loss-of-function experiments demonstrated that the PPARγ played an anti-inflammatory role in an autophagy-dependent manner. In addition, CSE administration inactivated the AMPK signaling, which was restored by PPARγ agonists. The effects of PPARγ agonists on inflammation and Autophagy could be abolished by AMPK Inhibitor. CONCLUSIONS We demonstrated that PPARγ played a protective role in CSE-induced inflammation and Autophagy by activating AMPK signaling in BECs, which may provide investigation basis for clinical therapy of chronic pulmonary diseases.