Exercise Ameliorates Emphysema Of Cigarette Smoke-Induced COPD In Mice Through The Exercise-Irisin-Nrf2 Axis

Abstract

Hiroaki Kubo, Kazuhisa Asai, Kazuya Kojima, Arata Sugitani, Yohkoh Kyomoto, Atsuko Okamoto, Kazuhiro Yamada, Naoki Ijiri, Tetsuya Watanabe, Kazuto Hirata, Tomoya Kawaguchi Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, JapanCorrespondence: Kazuhisa AsaiDepartment of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-Ku, Osaka 545-8585, JapanTel [phone]Fax [phone]Email [email protected]: Oxidative stress is one of the important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). Irisin is a type of myokine secreted from the muscle during exercise and acts against oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor with antioxidant properties. Here, we examined the emphysema suppressive effects of the exercise-irisin-Nrf2 axis in mice.Methods: Mice were divided into three groups, namely, the control, smoking, and exercise + smoking groups. All mice from the smoking and exercise + smoking groups were exposed to cigarette smoke once a day. The mice from the exercise + smoking group were adapted to a treadmill once a day. To investigate the Nrf2 cascade, after 12 weeks, serum irisin concentration and Nrf2 and heme oxygenase-1 (HO-1) expression in the lung homogenate were determined. To evaluate cigarette smoke-induced COPD, the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), mean linear intercept (MLI), and destructive index in the lung tissue were examined.Results: Serum irisin concentration and the expression levels of Nrf2 and HO-1 in the lung homogenate were significantly higher in mice from the exercise + smoking group than in those from the control and smoking groups. The proportion of neutrophils in the BALF was significantly lower in the exercise + smoking group than in the smoking group. The MLI and destructive index were also significantly smaller in mice from the exercise + smoking group than mice from the smoking group.Conclusion: Irisin secreted from the muscle during exercise may exert protective effects against oxidative stress via Nrf2 and HO-1, and ameliorate emphysema of cigarette smoke-induced COPD. The exercise-irisin-Nrf2 axis may serve as a novel target for COPD treatment.Keywords: chronic obstructive pulmonary disease, oxidative stress, exercise, irisin, nuclear factor erythroid 2-related factor 2, heme oxygenase-1  

Keywords

• chronic obstructive pulmonary disease
• oxidative stress
• exercise
• irisin
• nuclear factor erythroid 2-related factor 2
• heme oxygenase-1