Role of purinergic signaling in the antiinflammatory effects of aerobic training in a model of asthma induced by house dust mite

Abstract

Asthma is a chronic airway inflammatory disease that results in impairment of quality of life of asthmatics. In the last years, several studies have demonstrated that aerobic physical training (AT) performed properly results in anti-inflammatory effects to the airways, either in experimental models of asthma or to asthmatic individuals. Thus, the present project aims to evaluate the effects of AT in experimental models of asthma using house dust mite (HDM) (dermatophagoides pteronyssinus). To this purpose, in the experimental model of chronic asthma (HDM 100ug/mouse; 1x/week, 7 weeks), the animals will receive the HDM by intra-tracheal via during the first 3 weeks and then the AT will begin after the third week (for evaluation of the therapeutic effect of AT). The AT will be performed in a treadmill for mice, during 4 weeks, 1h/session, 5x/week. Twenty-four hours after the last session of training and HDM administration, the adenosine triphosphate (ATP) levels will be measured in the bronchoalveolar lavage (BAL), the number of cells (total and differential) in BAL and in blood, the number of eosinophils, macrophages and lymphocytes in the airways wall, the levels of pro-inflammatory mediators (Th2 cytokines - IL-4, IL-5 and IL-13 and also Th1 cytokine - TNF-alpha) and the levels of anti-inflammatory cytokines (IL-10, IL-1ra) in BAL and serum, the expression of sTNFR1 and sTNFR2 in the lungs, the expression of purinergic receptors (P2X7, P2Y2 and P2Y6) in the lungs and in the lymphatic organs (spleen, lymphnodes and bone marrow), as well as the airways remodeling and the bronchial hyperresponsiveness. In addition, the levels of IL-4, IL-5, IL-13, IL-10 and IL-1ra in the supernatant of cell culture of total cells from spleen, lymph nodes and bone marrow re-stimulated in vitro with HDM will be measured. (AU)