Inhalation of nicotine-containing electronic cigarette vapor exacerbates the features of COPD by inducing ferroptosis in βENaC-overexpressing mice.
Autor: | Han H; Department of Biology, Georgia State University, Atlanta, GA, United States., Meister M; Department of Nutrition, Georgia State University, Atlanta, GA, United States., Peng G; Department of Biology, Georgia State University, Atlanta, GA, United States., Yuan Y; Department of Biology, Georgia State University, Atlanta, GA, United States., Qiao J; Department of Chemistry, Georgia State University, Atlanta, GA, United States., Yang JJ; Department of Chemistry, Georgia State University, Atlanta, GA, United States., Liu ZR; Department of Biology, Georgia State University, Atlanta, GA, United States., Ji X; Department of Nutrition, Georgia State University, Atlanta, GA, United States. |
---|---|
Jazyk: | angličtina |
Zdroj: | Frontiers in immunology [Front Immunol] 2024 Jun 14; Vol. 15, pp. 1429946. Date of Electronic Publication: 2024 Jun 14 (Print Publication: 2024). |
DOI: | 10.3389/fimmu.2024.1429946 |
Abstrakt: | Introduction: Chronic obstructive pulmonary disease (COPD) is currently listed as the 3 rd leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood. Methods: In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics. Results: ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells. Discussion: Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Han, Meister, Peng, Yuan, Qiao, Yang, Liu and Ji.) |
Databáze: | MEDLINE |
Externí odkaz: |