Department of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
Department of Respiratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
Med Sci Monit. 2018 Jul 25;24:5168-5177. doi: 10.12659/MSM.909285.
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.
吸烟是多种慢性肺部疾病的已知危险因素。本研究旨在探讨过氧化物酶体增殖物激活受体（PPAR）γ在吸烟引起的炎症中的作用。
采用香烟烟雾提取物（CSE）诱导支气管上皮细胞（BEC）炎症。CSE 处理后，通过 Western blot 检测自噬相关蛋白（Beclin1、自噬相关基因（ATG）5、ATG7、p62 和 LC3）和 PPARγ水平。随后，用 PPARγ激动剂和拮抗剂处理 CSE 诱导的 BEC，检测几种炎症因子（白细胞介素（IL）-6、IL-8、诱导型一氧化氮合酶（iNOS）和环氧化酶（COX）-2）和自噬相关蛋白，以测量炎症和自噬水平。然后敲低 LC3 以验证自噬在 CSE 诱导的炎症中的作用。最后，检测 CSE 刺激的 BEC 中 AMP 激活蛋白激酶（AMPK）及其下游 S6 激酶（S6K）。
CSE 处理导致 BEC 中自噬不足和 PPARγ减少。PPARγ激动剂改善了 CSE 诱导的炎症，并促进了自噬的发展，这表现在炎症因子和自噬相关蛋白的变化上。功能丧失实验表明，PPARγ通过自噬依赖性途径发挥抗炎作用。此外，CSE 处理使 AMPK 信号失活，而 PPARγ激动剂则使其恢复。PPARγ 激动剂对炎症和自噬的作用可以被 AMPK 抑制剂所阻断。
我们证明，PPARγ 通过激活 BEC 中的 AMPK 信号，在 CSE 诱导的炎症和自噬中发挥保护作用，这可能为慢性肺部疾病的临床治疗提供研究基础。
