Different anti-remodeling effect of nilotinib and fluticasone in a chronic asthma model
The Korean Journal of Internal Medicine
;
: 1150-1158, 2016.
Artigo
em Inglês
| WPRIM
| ID: wpr-149543
ABSTRACT
BACKGROUND/AIMS:
Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling.METHODS:
We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge.RESULTS:
Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor β1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly.CONCLUSIONS:
These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Óvulo
/
Asma
/
Proteínas Tirosina Quinases
/
Líquido da Lavagem Broncoalveolar
/
Fatores de Crescimento Transformadores
/
Ovalbumina
/
Citocinas
/
Colágeno
/
Interleucina-4
/
Interleucina-5
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Feminino
/
Humanos
Idioma:
Inglês
Revista:
The Korean Journal of Internal Medicine
Ano de publicação:
2016
Tipo de documento:
Artigo
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