3B). Increased expressions of MMP-12 (Dolhnikoff et al., 2009) as well as TIMP-1 and TIMP-2 (Chiba et al., 2007) have been demonstrated in the airways of rats with allergic airway inflammation and also of asthmatic
patients, results which are in agreement with the findings of this study. Increased expression of matrix metalloproteinases (MMPs) are involved in the degradation of trans-isomer mw different extracellular proteins matrix (i.e. collagen, elastin, laminins and proteoglycans), leading some cell types (i.e. fibroblasts) to respond to abnormal production of proteins of extracellular matrix, causing fibrosis (Chiba et al., 2007, Davies, 2009 and Dolhnikoff et al., 2009). Then, the findings showed in the present study suggest that AE can modulate the expression MMPs and TIMPs, and further studies are necessary to elucidate the mechanisms involved in the response. Finally, we evaluated the epithelial
expression of P2X7 receptor (P2X7R) as a possible mechanism of AE regulating allergic GSK1210151A mw airway inflammation and remodeling. We found that sensitized animals presented a significant increase in the epithelial expression of P2X7R, whereas AE reduced its expression (Fig. 4), suggesting an inhibitory effect of AE on the upregulation of P2X7R induced by OVA. P2X7R is a plasma membrane receptor and a gated-channel/pore receptor that is activated by extracellular adenosine triphosphate (ATP) and expressed in lung epithelial cells (Burnstock et al., 2010, Ferrari et al., 2006 and Muller else et al., 2010).
P2X7R is involved in the regulation of the immune system, including the control of pro-inflammatory cytokines (Ferrari et al., 2006). A recent study demonstrated that P2X7R is upregulated and involved in the development of airway inflammation and remodeling (Muller et al., 2010). However, this is just the first demonstration that AE reduces P2X7R expression in animals with chronic allergic airway inflammation, and further studies using P2X7R knockout animals or specific P2X7R inhibitors (i.e. KN62) are necessary to better understand the possible role of P2X7R in the anti-inflammatory effects of AE on asthma. Thus, in the present study we cannot demonstrate the causal relationship between the AE-reduce P2X7R expression and its anti-inflammatory effects. Therefore, we conclude that aerobic exercise modulates the epithelial response in an animal model of asthma by reducing the epithelial expression of important pro-inflammatory and pro-fibrotic mediators, as well as by increasing expression of anti-inflammatory cytokine IL-10. However, additional studies aiming to investigate a causal relationship between these exercise-reduce epithelial expression of pro-inflammatory molecules are required.