IL-17F Induces IL-6 Via TAK1-NFκB Pathway in Airway Smooth Muscle Cells

Overview

Journal Immun Inflamm Dis

Specialties Allergy & Immunology
Infectious Diseases

Date 2017 May 6

PMID 28474507

Citations 7

Authors

Masayuki Nakajima

Mio Kawaguchi

Kyoko Ota

Junichi Fujita

Satoshi Matsukura

Shau-Ku Huang

Yuko Morishima

Yukio Ishii

Hiroaki Satoh

Tohru Sakamoto

Nobuyuki Hizawa

Affiliations

Soon will be listed here.

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.

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