The exacerbation of asthma is often caused by airway infections, resulting the corticosteroid resistance and the difficulty to control asthma symptoms. Recently, it was reported that Src was involved in inflammatory responses. We also reported that dasatinib (DAS), a Src inhibitor, suppressed corticosteroid insensitive airway inflammation of mice induced by lipopolysaccharide. Thus, we determined effects of DAS on airway inflammation of mice induced by house dust mite (HDM) and poly(I:C).
Mice, sensitized to HDM, were intranasally challenged with HDM once every other day for 11 days, followed by treatment with DAS or fluticasone propionate (FP) twice daily for 3days. Some mice were also exposed to poly(I:C) 2hr after each drug treatment. One day after the last drug treatment, bronchoalveolar lavage fluid (BALF) was collected. The numbers of eosinophils and neutrophils, and the levels of CXCL1, IL-13 and IL-33 in BALF were measured.
DAS suppressed the increases in inflammatory cells and cytokine/chemokine levels induced by HDM alone and HMD + poly(I:C), whereas FP had little effects on these increases induced by HDM + poly(I:C). These results suggested that Src will be one of the important therapeutic target for asthma and its exacerbation.
This study was partly supported by Nihon Univ. Multidisciplinary Research Grant for 2021.