Mitoquinone ameliorates cigarette smoke-induced airway inflammation and mucus hypersecretion in mice
Autor: | Deqing Yang, Tao Wang, Lian Liu, Fuqiang Wen, Zhicheng Yuan, Yongchun Shen, Dan Xu |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Ubiquinone medicine.medical_treatment Immunology Anti-Inflammatory Agents Inflammation medicine.disease_cause Antioxidants 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Organophosphorus Compounds Internal medicine Smoke medicine Immunology and Allergy Animals Lung Pharmacology MitoQ Secretory Pathway NF-kappa B Pneumonia Tobacco Products respiratory system Malondialdehyde Mucus Mitochondria Mice Inbred C57BL IκBα Disease Models Animal Oxidative Stress 030104 developmental biology Cytokine Endocrinology chemistry 030220 oncology & carcinogenesis Respiratory epithelium Cytokines medicine.symptom Inflammation Mediators Oxidative stress Signal Transduction |
Zdroj: | International immunopharmacology. 90 |
ISSN: | 1878-1705 |
Popis: | Background Cigarette smoking, which induces airway inflammation and mucus hypersecretion, is a major risk factor for the development of cigarette smoke (CS)-induced airway disorders. In this study, we investigated the effects and mechanisms of mitoquinone (MitoQ), a mitochondria-targeted antioxidant, on CS-induced airway inflammation and mucus hypersecretion in mice. Methods C57BL/6J mice were exposed to CS for 75 min twice daily, 5 days per week for 4 weeks. MitoQ (2.5, 5 mg/kg/day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was obtained for cell counting and determination of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination; Western blotting was used to measure levels of Mfn2, Drp1, cytochrome c, NF-κB p65, and IκBα. Results Pretreatment with MitoQ significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, goblet cell hyperplasia and Muc5ac staining. The numbers of total cells, neutrophils and macrophages, as well as levels of TNF-α and IL-6 in BALF were remarkably decreased by MitoQ in a dose-dependent manner. MitoQ attenuated oxidative stress by preventing the CS-induced increase in malondialdehyde level and decrease in superoxide dismutase activity and GSH/GSSG ratio. MitoQ decreased the expression of mitochondrial fission protein Drp1 and increased that of mitochondrial fusion protein Mfn2, as well as reduced cytochrome c release into the cytosol. Furthermore, MitoQ suppressed IκBα degradation and NF-κB p65 nuclear translocation. Conclusions MitoQ attenuates inflammation, mucus hypersecretion, and oxidative stress induced by CS. It may exert these effects in part by modulating mitochondrial function and the NF-κB signal pathway. |
Databáze: | OpenAIRE |
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