IL-17F induces IL-6 via TAK1-NFκB pathway in airway smooth muscle cells.
Immun Inflamm Dis
; 5(2): 124-131, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-28474507
ABSTRACT
INTRODUCTION:
Interleukin (IL)-17F plays a critical role in the pathophysiology of asthma. However, the precise role of IL-17F in airway smooth muscle cells (ASMCs) and its regulatory mechanisms remain to be defined. Therefore, we sought to investigate the expression of IL-6 by IL-17F and the involvement of transforming growth factor ß-activated kinase 1 (TAK1) and nuclear factor (NF)-κB by in ASMCs.METHODS:
ASMCs were cultured in the presence or absence of IL-17F. The expression of IL-6 gene and protein was analyzed using real-time PCR and ELISA, and the activation of TAK1 and NF-κB was detected by Western blotting. The effect of TAK1 inhibitor 5Z-7-oxozeaenol and NF-κB inhibitor BAY 11-7082 on the expression of IL-6 was investigated. Finally, the short interfering RNAs (siRNAs) targeting TAK1 and a subunit of NF-κB, p65 were transfected into ASMCs.RESULTS:
The expression of IL-6 gene and protein was significantly induced by IL-17F. IL-17F activated TAK1 and NF-κB in ASMCs. Transfection of siRNAs targeting TAK1 abolished IL-17F-induced phosphorylation of p65. Both 5Z-7-oxozeaenol and BAY 11-7082 significantly inhibited IL-17F-induced IL-6 production in a dose-dependent manner. Similarly, transfection of the cells with siRNAs targeting TAK1 and p65 inhibited the expression of IL-6.CONCLUSIONS:
Collectively, these results provided evidence supporting the potential importance of the Th17-ASMCs crosstalk via the IL-17F-IL-6 axis in airway inflammation and as a candidate pharmacological target for airway inflammatory diseases such as asthma.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Interleucina-6
/
Interleucina-17
/
MAP Quinase Quinase Quinases
/
Sistema de Sinalização das MAP Quinases
/
Miócitos de Músculo Liso
Limite:
Humans
Idioma:
En
Revista:
Immun Inflamm Dis
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão