RU486 blocks the anti-inflammatory effects of exercise in a murine model of allergen-induced pulmonary inflammation

Abstract

In an ovalbumin (OVA)-driven murine model of allergic pulmonary inflammation, we have shown previously that moderate-intensity aerobic exercise training attenuates inflammatory responses, disease progression, and NF-κB activation within the sensitized lung. Glucocorticoids (GCs), potent anti-inflammatory agents, have been shown to alter transcriptional events that are important in asthmatic pathogenesis, such as NF-κB activation. Notably, exercise training can alter the production and signaling capacity of endogenous GCs. Because GCs exert their anti-inflammatory effects through binding to intracellular glucocorticoid receptors (GRs), we examined the role of the GR in facilitating the anti-inflammatory effects of exercise. Results show that, in exercised OVA-sensitized mice, treatment with the GR antagonist RU486 blocked the exercise-induced reductions in cellular infiltration of the airways (p < .05), KC and soluble VCAM-1 protein levels in the bronchoalveloar lavage fluid (p < .05), and NF-κB translocation and DNA binding within the lung to levels similar to those observed in sedentary OVA-sensitized mice. Importantly, RU486 treatment also blocked exercise-induced increases in GR nuclear translocation to the levels seen in sensitized control mice. Together, these results suggest that GR nuclear translocation and NF-κ activation play roles in mediating the anti-inflammatory effects of exercise in allergen-mediated lung pathology.

Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling

“…These clinical benefits have also suggested a possible anti-inflammatory effect of aerobic training on asthma. Only few studies have investigated the anti-inflammatory effects of aerobic training on asthma, using an allergic murine model (40,41,61). In accordance with these studies, the anti-inflammatory effects of aerobic exercise could be attributed to decreased levels of IL-4, IL-5, IgE and also an increase in the antiinflammatory cytokine IL-10 (40,41,61).…”

“…In previous studies, our and other groups have observed that low-and moderate-intensity aerobic exercise specifically decreases airway eosinophilic inflammation and remodeling (40,41,61). Recently, we demonstrated that low-and moderateintensity aerobic training decreases airway inflammation and remodeling in an experimental model of chronic allergic lung inflammation in mice and that these effects are not mediated by increased Th 1 response but could be partially mediated by increased interleukin (IL)-10 expression (61).…”

“…Although few studies have investigated the effects of lowand moderate-intensity aerobic exercise on allergic immune responses, particularly on vascular and parenchymal inflammation, only Pastva et al (40,41) evaluated these pulmonary compartments. Therefore, this study evaluated the hypothesis that low and moderate aerobic exercise could decrease perivascular and parenchymal inflammation and vascular tissue remodeling in a mouse model of chronic allergic lung inflammation (61,62).…”

Has Aerobic Exercise Anti-inflammatory Effect for Asthma?

“…Shortly, these studies have demonstrated that these beneficial effects can be attributed to decreased activation of leukocytes and bronchial epithelial cells as a result of increased activation of glucocorticoids receptors, T-regulatory cells resulting in increased synthesis of anti-inflammatory cytokine IL-10, and decreased activation of transcriptional factor NF-kB [16][17][18][19][20][21][22][23][24]. In addition, these studies also demonstrated that aerobic exercise present a direct inhibitory effect on the pulmonary oxidants production as well as on the synthesis of mediators involved in the airway remodeling process [19,24].…”

“…In this direction, since 2004 a growing number of experimental studies using mouse models of chronic allergic airway inflammation have demonstrated that low and moderate intensity aerobic exercise performed either before, during or after the allergen sensitization results in decreased eosinophilic inflammation, Th2 cytokines production, airway remodeling and hyperresponsiveness [16][17][18][19][20][21][22][23][24]. Shortly, these studies have demonstrated that these beneficial effects can be attributed to decreased activation of leukocytes and bronchial epithelial cells as a result of increased activation of glucocorticoids receptors, T-regulatory cells resulting in increased synthesis of anti-inflammatory cytokine IL-10, and decreased activation of transcriptional factor NF-kB [16][17][18][19][20][21][22][23][24].…”