Aerobic exercise training reduces asthma phenotype via inhibition of accumulation of extracellular ATP mediated by P2X7 receptor

Abstract

Asthma is a chronic allergic inflammatory disease mediated by different mediators. Adenosine triphosphate (ATP) has emmerged as a pivotal mediator of accute and chronic asthmatic reactions, by activation of purinergic receptors. Aerobic exercise (AT) reduces allergic airway inflammation, but the mechanisms are unknown. Thus, this study investigated the effects of AT in a model of ovalbumin induced asthma. For this purpose, 40 C57Bl/6 mice were distributed in Control, Exercise, OVA and OVA+Exercise groups. AT was performed in a treadmill, 5x/week, 1h/session, 60% of maximal exercise capacity, during 4 weeks after the establishment of chronic allergic airway inflammation (10ug ovalbumin i.p. on days 0, 14, 28 and 42 and 1% ovalbumin aerosol challenge 3x/week begining on day 21 until day 53). AT in asthma group (OVA+AT) reduced the levels of extracellular ATP in BAL (p<0.05) (measured through chemiluminescence) and also reduced the expression of P2X7 receptor in the lungs (p<0.001) (evaluated by western blotting). In addition the expression of P2X7 receptor was also evaluated by immunohistochemistry and revealed that AT reduces P2X7 receptor expression in airway epithelial cells. OVA+AT group also presented reduced the number of total cells (p<0.01) and eosinophils (p<0.01) in BAL as well as the levels of IL-5 in BAL (p<0.01), serum (p<0.01), while increased the levels of IL-10 in BAL (p<0.01) and serum (p<0.01). Of note, OVA+AT also presented reduced hyperresponsivenes to 25 and 50mg/mL of metacholine (p<0.05). In conclusion, AT reduces asthma phenotype by reducing extracellular ATP accumulation resulting in diminished P2X7 receptor expression.