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

• Published in: Brain, behavior, and immunity behavior, and immunity, 2005-09, Vol.19 (5), p.413-422
• Main Authors: Pastva, Amy, Estell, Kim, Schoeb, Trenton R., Schwiebert, Lisa M.
• Format: Article
• Language: English
• Subjects: Aerobiosis; Allergens - toxicity; Animals; Asthma; Bronchoalveolar Lavage Fluid - cytology; DNA - metabolism; Electrophoretic Mobility Shift Assay; Exercise; Female; Glucocorticoids; Hormone Antagonists - pharmacology; Inflammation; Inflammation - physiopathology; Interleukin-8 - metabolism; Mice; Mice, Inbred BALB C; Mifepristone - pharmacology; NF-kappa B - antagonists & inhibitors; NF-kappa B - physiology; NF-κB; Ovalbumin - immunology; Physical Conditioning, Animal - physiology; Physical Exertion - physiology; Pneumonia - pathology; Pneumonia - physiopathology; Receptors, Glucocorticoid - antagonists & inhibitors; Receptors, Glucocorticoid - physiology; RU486; Sample Size; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2005.04.004

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-κB activation play roles in mediating the anti-inflammatory effects of exercise in allergen-mediated lung pathology.