Lipopolysaccharide及びovalbuminにより誘発した気道炎症に対するdasatinibの効果

抄録

Corticosteroid insensitive airway inflammation is observed in some patients of chronic obstructive pulmonary disease (COPD) and severe asthma. We previously reported that repeated dosed lipopolysaccharide (LPS) reduced corticosteroid sensitivity in mice. Recently, some groups reported that Src was involved in inflammatory responses in mice models of COPD and asthma. Thus, we determined effects of dasatinib on airway inflammation in mice induced by ovalbumin (OVA) and/or LPS exposure.

Mice were sensitized to OVA twice every 7 days and challenged with OVA once every other day for 11 days. Mice, sensitized/challenged or naïve to OVA, were exposed to LPS and treated with dasatinib or fluticasone propionate (FP) twice daily for 3 days. One day after the last LPS exposure, bronchoalveolar lavage fluid (BALF) was collected. The number of inflammatory cells, and CXCL1 and TNF-α levels in BALF were measured by flow cytometry and ELISA, respectively.

LPS alone or OVA and LPS exposure caused increases in the number of inflammatory cells, and CXCL1 and TNF-α levels in BALF. Dasatinib suppressed both of these airway inflammation, but FP did not. These results suggest that Src was important for inflammatory responses. Therefore, the Src inhibitor will provide new therapeutic agents for corticosteroid insensitive airway inflammation.