INVOLVEMENT OF PURINERGIC SIGNALING AND LYMPHOID ORGANS IN THE BENEFICIAL EFFECTS OF AEROBIC TRAINING IN ASTHMA

Abstract

PURPOSE: Asthma is a chronic airway inflammatory disease affecting more than 300 million people around the world. Purinergic signaling via purinergic receptors (mainly P2X7, P2Y2 and P2Y6) are thought play a key role in asthma pathogenesis and severity. High intensity aerobic exercise is known to trigger asthma attacks, while low to moderate intensity training reduces inflammation and improves asthma control. Therefore, this study investigated whether low intensity aerobic exercise reduces asthma phenotype by modulation of purinergic signaling. METHODS: Aerobic exercise (AE) was performed in a treadmill at low intensity, 5x/week, 1h/session, for 4 weeks, beginning 2 weeks after HDM administration. HDM (dermatophagoides pteronyssinus; 100mg/mouse) was administered 3x/week, for 6 weeks. RESULTS: The results demonstrated that AE reduced adenosine triphosphate (ATP) accumulation (p<0.001), IL-1beta, IL-4, IL-5, CXCL1/KC, IL-13, IL-17, IL-23, IL-33 and TNF-alpha (p<0.001), while increased IL-1ra, IL-2, IL-10 and IL-12p40 in bronchoalveolar lavage (BAL). Total number of leukocytes, eosinophils, lymphocytes and neutrophils in BAL and the number of eosinophils, neutrophils and lymphocytes in the airway wall (p<0.01) were reduced by AE. Airway remodeling (collagen, elastin, smooth muscle and mucus) were reduced by AE (p<0.01). TGF-beta, IGF-1 and VEGF levels was reduced by AE (p<0.001). Lung mechanics (Resistance, Elastance, GTIS, HTIS, RAW) and airway hyperresponsiveness (AHR) to methacholine was ameliorated by AE (p<0.01). IL-4, IL-5 and IL-13 production by re-stimulated mediastinal lymph nodes, splenocytes and bone marrow cells was also reduced by AE. The expression of P2X7, P2Y2 and P2Y6 by peribronchial leukocytes (p<0.01) and also by airway epithelial cells (p<0.01) were reduced by AE. CONCLUSIONS: Low intensity aerobic training reduces asthma phenotype by inhibiting purinergic signaling and lymphoid organs hyperactivation.