Exercise Improves Lung Inflammation, but Not Lung Remodeling and Mechanics in a Model of Bleomycin-Induced Lung Fibrosis

Abstract

Introduction. Moderate aerobic exercise training accelerates the resolution of lung fibrosis in a model of bleomycin-induced pulmonary fibrosis. However, whether it can inhibit the development of lung fibrosis is unknown. Materials and Methods. C57Bl/6 mice were distributed into four groups: Control (Co), Exercise (Exe), Bleomycin (Bleo), and Bleomycin+Exercise (Bleo+Exe). A single bleomycin dose (1.5 UI/kg) was administered orotracheally and treadmill exercise started in the same day, enduring for 4 weeks, 5x/week, 60 minutes/session, at moderate intensity. Lung mechanics, systemic and pulmonary inflammation, and lung remodeling were evaluated. Lung homogenates were used to evaluate the antioxidant status. Results. Total cells, macrophages, lymphocytes, and neutrophils numbers, in agreement with IL-6 levels, were higher in the BAL and serum of Bleo group, compared to other groups. In addition, lung levels of LTB4 in Bleo were higher than other groups, whereas SOD activity and nitric oxide levels in exercised groups (Exe and Exe+Bleo) compared to the Bleo group. Lung GPX activity was lower in Bleo and Exe+Bleo groups compared to others. Exe and Exe+Bleo groups also showed higher IL-10 expression by lung macrophages than other groups, whereas TGF-β expression was higher in Exe, Bleo, and Exe+Bleo groups compared to control. CCR7 expression was induced only in the Exe group. However, exercise did not improve lung remodeling and mechanics, or serum and pulmonary levels of VEGF, IGF-1, and TGF-β. Conclusion. Aerobic exercise training initiated concomitantly with induction of pulmonary fibrosis reduces lung and systemic inflammation but fails to inhibit lung fibrosis and mechanics impairment.

αCGRP deficiency aggravates pulmonary fibrosis by activating the PPARγ signaling pathway

“…The G protein-coupled receptor CysLT2, a LT receptor, is involved in inflammatory pain, and CysLT2 mRNA is positive for transient receptor potential vanilloid 1 (TRPV1), which releases CGRP and is highly colocalized with neurons [ 39 ]. Recent studies have also found that high levels of LTB4, a key endogenous molecule that induces the neutrophil inflammatory response, are associated with PF [ 40 ], and LTB4 biosynthesis blockade is now a potential strategy for the treatment of IPF and cystic PF [ 41 , 42 ]. Therefore, we speculate that upregulated lipid oxidation in Calca -KO animals might be an important contributor to the development of PF in these models.…”

Bioinformatics Analysis Identifies Potential Ferroptosis Key Genes in the Pathogenesis of Pulmonary Fibrosis

“…Interestingly, our animal experiment showed that CAV1 mRNA expression increased when treadmill exercise was performed in mice with pulmonary fibrosis. El-Mafarjeh et al ( El-Mafarjeh et al, 2020 ) showed that treadmill exercise improves pulmonary and systemic inflammation in bleomycin-induced pulmonary fibrosis models. This may be related to the fact in this study that treadmill increases CAV1, but the specific mechanisms need to be confirmed by further experiments.…”

Chemotherapy‐induced toxicity in patients with testicular germ cell tumors: The impact of physical fitness and regular exercise

“…127 In terms of lung fibrosis and inflammation, 4 weeks of moderate intensity (60minutes, 5 times per week) treadmill running improved lung and systemic inflammation, but it did not inhibit bleomycin-induced lung fibrosis and remodeling in an animal study. 128 Others, however, have observed also accelerated resolution of lung fibrosis (reduced collagen fiber depositions) following 4-week exercise training in mice with bleomycin-induced lung fibrosis. 129…”

“…Importantly, better results can be achieved when patients: (i) have more than 20 minutes of high intensity exercise in each session of aerobic training interventions, (ii) started to exercise prior to the treatment, and (iii) exercised for > 8 weeks in duration 127 . In terms of lung fibrosis and inflammation, 4 weeks of moderate intensity (60minutes, 5 times per week) treadmill running improved lung and systemic inflammation, but it did not inhibit bleomycin‐induced lung fibrosis and remodeling in an animal study 128 . Others, however, have observed also accelerated resolution of lung fibrosis (reduced collagen fiber depositions) following 4‐week exercise training in mice with bleomycin‐induced lung fibrosis 129 …”