Chronic obstructive pulmonary disease (COPD) is characterized by corticosteroid insensitive airway inflammation. Tobacco smoke (TS) induces oxidative stress and activation of Src, which cause airway inflammation. Recently, we reported that dasatinib (DAS), a Src inhibitor, suppressed airway inflammation in mice induced by lipopolysaccharide. Then, in this study, we determined the effects of DAS alone and the combination with quercetin, an antioxidant agent, on TS induced airway inflammation.
　A/J mice were exposed to TS for 11 days, followed by intranasal treatments with DAS, quercetin and fluticasone propionate (FP) twice daily for 3 days. Bronchoalveolar lavage fluid (BALF) was collected one day after the last drug treatment, and the numbers of inflammatory cells in BALF were measured by hemocytometers and a flow cytometer.
　TS induced the significant increases in the numbers of neutrophils and macrophages in BALF, and FP had no effect on these increases. DAS improved the corticosteroid insensitive airway inflammation in mice induced by TS. In addition, the combination of DAS with quercetin showed further suppressive effects on airway inflammation in mice than DAS alone. These results suggested that the combination of Src inhibitors with antioxidant agents may be a novel therapeutic strategy for the treatment of COPD.