Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA

Autor: Yuki Nishimoto, Daiki Ando, Kosuke Irie, Ikumi Kainuma, Yuki Katayama, Shiori Sato, Tomohiro Suzuki, Mai Harada, Tsubasa Yoshida, Kazuhiro Ito, Yasuo Kizawa
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Biochemistry and Biophysics Reports, Vol 33, Iss , Pp 101402- (2023)
Druh dokumentu: article
ISSN: 2405-5808
DOI: 10.1016/j.bbrep.2022.101402
Popis: Asthma exacerbation is a significant clinical problem that causes resistance to corticosteroid therapy and elevated hospitalization risk. Src family kinases (SFKs) contribute to various steps of the immune response, such as airway inflammation in viral or bacterial infections and allergic asthma. Therefore, we determined the effects of dasatinib (DAS), a typical Src inhibitor, on a murine asthma exacerbation model induced by house dust mites (HDM) and synthetic analog of double-stranded RNA, poly(I:C). A/J mice were sensitized to intrapreneurial HDM twice every seven days and challenged with intranasal HDM once every second day for a total of six exposures, and/or exposed to poly(I:C) twice daily for three consecutive days. Drug treatments were performed twice daily for three days, starting one day after the last HDM challenge or 2 h before each poly(I:C) exposure. DAS improved poly(I:C)-induced acute inflammation dose-dependently. Both DAS and fluticasone propionate (FP) attenuated HDM-induced allergic airway inflammation. However, in HDM and poly(I:C) induced-asthma exacerbated mice, DAS significantly improved inflammatory cells in bronchoalveolar lavage fluid and histological changes in the lungs, whereas FP did not. Therefore, SFKs are important targets for controlling severe asthma refractory to conventional therapies.
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