Ovalbumin 及び lipopolysaccharide によって誘発したマウスの喘息急性増悪モデルに対する Src 阻害薬の抗炎症作用

Asthma is often exacerbated by airway infection, and some patients with severe asthma may be unresponsive to conventional corticosteroid treatment. Src family kinases (SFKs) were recently implicated in the inflammatory responses of mice induced by allergen and bacterial toxin lipopolysaccharide (LPS). Therefore, we examined the effects of dasatinib (DAS), a Src inhibitor, on airway inflammation in mice induced by ovalbumin (OVA) and LPS. Male A/J mice were sensitized to OVA Day -14 and -7, challenged with intranasal OVA on Day 0, 2, 4, 6 and 8, and on Day 10, mice were also challenged with OVA via inhalation. Mice were treated intranasally with DAS or fluticasone propionate (FP), a glucocorticoid, twice daily for 3d starting 1d after OVA inhalation. Moreover, some mice were also administrated LPS 2h after DAS or FP treatment to model of asthma exacerbation. One day after the last intervention, lung tissue and bronchoalveolar lavage fluid (BALF) were collected. DAS attenuated the accumulation of inflammatory cells and cytokines/chemokines in BALF induced by both OVA and OVA+LPS, while FP did not reduce accumulations induced by OVA+LPS. Therefore, targeting SFKs may be a superior therapeutic approach for asthma exacerbation by infection.