Exercise training restores bleomycin-induced downregulation of pulmonary CBS/CSE expression, thus contributing to the increased H S generation and suppression of TGF-β1/Smad and LRP-6/β-catenin signalling pathways, EMT and lung fibrosis.
Exercise training is advocated for treating chronic inflammation and obesity-related metabolic syndromes. Glucocorticoids (GCs), the anti-inflammatory hormones, are synthesized or metabolized in extra-adrenal organs. This study aims to examine whether exercise training affects obesity-associated pulmonary inflammation by regulating local GC synthesis or metabolism. We found that sedentary obese () mice exhibited increased levels of interleukin (IL)-1β, IL-18, monocyte chemotactic protein (MCP)-1, and leukocyte infiltration in lung tissues compared with lean mice, which was alleviated by 6 wk of exercise training. Pulmonary corticosterone levels were decreased in mice. Exercise training increased pulmonary corticosterone levels in both lean and mice. Pulmonary corticosterone levels were negatively correlated with IL-1β, IL-18, and MCP-1. Immunohistochemical staining of the adult mouse lung sections revealed positive immunoreactivities for the steroidogenic acute regulatory protein, the cholesterol side-chain cleavage enzyme (CYP11A1), the steroid 21-hydroxylase (CYP21), 3β-hydroxysteroid dehydrogenase (3β-HSD), and type 1 and type 2 11β-hydroxysteroid dehydrogenase (11β-HSD) but not for 11β-hydroxylase (CYP11B1). Exercise training significantly increased pulmonary 11β-HSD1 expression in both lean and mice. In contrast, exercise training per se had no effect on pulmonary 11β-HSD2 expression, although pulmonary 11β-HSD2 levels in mice were significantly higher than in lean mice. RU486, a glucocorticoid receptor antagonist, blocked the anti-inflammatory effects of exercise training in lung tissues of obese mice and increased inflammatory cytokines in lean exercised mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local GC activation and suppression of pulmonary inflammation in obese mice. Treadmill training leads to a significant increase in pulmonary corticosterone levels in mice, which is in parallel with the favorable effects of exercise on obesity-associated pulmonary inflammation. Exercise training increases pulmonary 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression but has no significant effect on 11β-HSD2 expression in both lean and mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local glucocorticoid activation and suppression of pulmonary inflammation in obese mice.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.