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Immun Inflamm Dis. 2017 Jun;5(2):124-131. doi: 10.1002/iid3.149. Epub 2017 Mar 3.

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

Author information

1
Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
2
Respiratory Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan.
3
Asthma and Allergy Center, Johns Hopkins University, Baltimore, Maryland, USA.
4
National Health Research Institutes, Taipei, Taiwan.

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 β-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.

KEYWORDS:

IL-17F; NF-κB; TAK1

PMID:
28474507
PMCID:
PMC5418132
DOI:
10.1002/iid3.149
[Indexed for MEDLINE]
Free PMC Article

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