title: 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-kappaB 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-kappaB 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-kappaB 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-kappaB activation play roles in mediating the anti-inflammatory effects of exercise in allergen-mediated lung pathology.
authors.affiliation: Department of Physiology and Biophysics, University of Alabama at Birmingham, 35294-0005, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Pastva
authors.forename: Kim
authors.initials: K
authors.lastname: Estell
authors.forename: Trenton R
authors.initials: TR
authors.lastname: Schoeb
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Schwiebert
mesh_terms: D000332:Aerobiosis; D000485:Allergens / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology*; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D011014:Pneumonia / Q000473:pathology / Q000503:physiopathology*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology; D018401:Sample Size; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000485:Allergens; D006727:Hormone Antagonists; D016209:Interleukin-8; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D019010:Vascular Cell Adhesion Molecule-1; D015735:Mifepristone; D010047:Ovalbumin; D004247:DNA