Activation of TGFbeta/Smad signaling pathway in induced sputum of asthmatic children

Airway remodeling has been shown to be present very early in the course of childhood asthma. TGF? has been implicated in the mechanisms leading to airway restructuring processes. To evaluate the relationship between proinflammatory and proremodeling mediators and the severity and control of asthma in children, the TGF?1 levels in sputum supernatants, the expression of phosphorylated Smad2 in sputum cells (SC), the number of sputum eosinophils as well as the FeNO levels, were evaluated in 12 intermittent (IA), in 23 moderate (MA) asthmatic children, and in 9 controls (C). TGF-?1 sputum concentrations were increased in IA (no sta- tistically significant) and MA (p<0.0036) when compared to C. Immunostainings showed that the percentage of SC positive for p-Smad2 was higher in IA and MA than in C. FeNO and the number of sputum eosinophils were increased in IA and MA in comparison to C. Finally, in MA, sputum eosinophilia positively correlated with FeNO, TGF?1, and asthma duration. The increased expression of p-Smad2 and TGF?1 levels suggests an involvement of TGF?/Smad signaling pathway in the regulation of inflammatory response in asthmatic children. Moreover, this study shows that, in MA, inhaled corticosteroids do not completely inhibit all inflammatory cellular and molecular mechanisms in- volved in airway inflammation. The presence of profibrotic cytokines, such as TGF?1, concomitantly with FeNO and sputum eosinophilia, indicates that re- modeling mediators may be released simultaneously with inflammatory mediators other than consecutively in asthmatic children.