Journal Article IL-17F induces IL-6 via TAK1-NFκB pathway in airway smooth muscle cells

Nakajima, Masayuki  ,  Kawaguchi, Mio  ,  Ota, Kyoko  ,  Fujita, Junichi  ,  Matsukura, Satoshi  ,  Huang, Shau-Ku  ,  Morishima, Yuko  ,  Ishii, Yukio  ,  Satoh, Hiroaki  ,  Sakamoto, Tohru  ,  Hizawa, Nobuyuki

5 ( 2 )  , pp.124 - 131 , 2017-06 , WILEY
IntroductionInterleukin (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 β-activated kinase 1 (TAK1) and nuclear factor (NF)-κB by in ASMCs.MethodsASMCs 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.ResultsThe 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.ConclusionsCollectively, 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.

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