Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA
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. Th...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580822002023 |
| _version_ | 1811167261016195072 |
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| author | Yuki Nishimoto Daiki Ando Kosuke Irie Ikumi Kainuma Yuki Katayama Shiori Sato Tomohiro Suzuki Mai Harada Tsubasa Yoshida Kazuhiro Ito Yasuo Kizawa |
| author_facet | Yuki Nishimoto Daiki Ando Kosuke Irie Ikumi Kainuma Yuki Katayama Shiori Sato Tomohiro Suzuki Mai Harada Tsubasa Yoshida Kazuhiro Ito Yasuo Kizawa |
| author_sort | Yuki Nishimoto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T16:07:28Z |
| format | Article |
| id | doaj.art-bc769493b78d48329e6372216d805cae |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-04-10T16:07:28Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-bc769493b78d48329e6372216d805cae2023-02-10T04:22:43ZengElsevierBiochemistry and Biophysics Reports2405-58082023-03-0133101402Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNAYuki Nishimoto0Daiki Ando1Kosuke Irie2Ikumi Kainuma3Yuki Katayama4Shiori Sato5Tomohiro Suzuki6Mai Harada7Tsubasa Yoshida8Kazuhiro Ito9Yasuo Kizawa10Laboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, JapanNational Heart and Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, United KingdomLaboratory of Physiology and Anatomy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, 274-8555, Japan; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405580822002023Src family kinaseCorticosteroid resistanceAsthmaExacerbation |
| spellingShingle | Yuki Nishimoto Daiki Ando Kosuke Irie Ikumi Kainuma Yuki Katayama Shiori Sato Tomohiro Suzuki Mai Harada Tsubasa Yoshida Kazuhiro Ito Yasuo Kizawa Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA Biochemistry and Biophysics Reports Src family kinase Corticosteroid resistance Asthma Exacerbation |
| title | Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA |
| title_full | Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA |
| title_fullStr | Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA |
| title_full_unstemmed | Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA |
| title_short | Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA |
| title_sort | dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsrna |
| topic | Src family kinase Corticosteroid resistance Asthma Exacerbation |
| url | http://www.sciencedirect.com/science/article/pii/S2405580822002023 |
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