Effect of inhaled budesonide on surfactant protein expression in asthmatic mice.

Pulmonary surfactant dysfunction may significantly contribute to small airway obstruction during the asthmatic response. Inhaled corticosteroids have been routinely used in the treatment of asthma, but neither its exact role nor its regulation on pulmonary surfactant is completely understood. The aim of this study was to determine the effect of budesonide on surfactant protein (SP) expression in asthmatic mice. Moreover, we investigated the function of transforming growth factor (TGF) beta signaling in the pulmonary surfactant system to identify a novel target for the treatment of asthma. Mice were sensitized and challenged by ovalbumin (OVA) to establish a murine model of asthma. To assess the effect of budesonide on asthmatic mice, animals were treated with aerosolized budesonide before OVA challenge. The levels of TGF-beta(1) in bronchoalveolar lavage fluid were analyzed by ELISA. The expressions of TGF-beta type I receptor, TGF-beta type II receptor, Smad2/3, Smad4, Smad7, and SPs were measured by immunochemistry technique and computerized image analysis system. SP-A and SP-B were significantly decreased after allergic sensitization and challenge, accompanied by active TGF-beta/Smad signal transduction. A dramatic increase in the expressions of SP-A and SP-B was observed after budesonide treatment. This was also accompanied by up-regulation of Smad7 expression and down-regulation of TGF-beta type I receptor expression. A possible explanation for the result is that an early budesonide inhaled treatment inhibits TGF-beta-induced reduction of SP-A and SP-B expression through inhibition of active TGF-beta/Smad signal transduction pathway in asthmatic mice. TGF-beta signaling may be a potentially important therapeutic target for antiasthma drugs.