In vitro study of the role of FOXO transcription factors in regulating cigarette smoke extract-induced autophagy.

摘要: Cigarette smoking is the chief etiological factor for chronic obstructive pulmonary disease (COPD). Oxidative stress induced by cigarette smoke (CS) causes protein degradation, DNA damage, and cell death, thereby resulting in acute lung injury (ALI). In this regard, autophagy plays a critical role regulating inflammatory responses maintaining organelle homeostasis cellular viability. Expression of autophagy-related proteins (ARPs) is regulated fork head box class O (FOXO) transcription factors. current study, we examined FOXO family proteins—FOXO1 FOXO3a—in CS extract (CSE)-induced autophagy. Using human adenocarcinoma cells with type II alveolar epithelial characteristics (A549), observed CSE-mediated downregulation FOXO3a. contrast, there was pronounced increase expression FOXO1 at both transcriptional translational levels CSE-challenged compared controls. Interestingly, knockdown FOXO3a heightened cytokines/chemokines (IL-6, IL-8, and MCP-1), ARPs, factor. Moreover, rescued upregulation ARPs A549 cells. addition, using ROS inhibitor N-acetyl-L-cysteine (NAC), abrogated mRNA several production MCP-1, CCL-5) suggesting an important CSE-induced Chromatin immunoprecipitation demonstrated increased binding the former to promoter regions genes- BECLIN1, ATG5, ATG12, ATG16, LC3 CSE challenged These findings suggest these genes during exposure. Overall, our provide evidence FOXO3a-dependent FOXO1-mediated regulation