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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 activ ated 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.

Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalImmunity Inflammation and Disease
Volume5
Issue number2
DOIs
Publication statusPublished - Jan 1 2017
Externally publishedYes

Keywords

  • IL-17F
  • NF-kB
  • TAK1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nakajima, M., Kawaguchi, M., Ota, K., Fujita, J., Matsukura, S., Huang, S. K., Morishima, Y., Ishii, Y., Satoh, H., Sakamoto, T., & Hizawa, N. (2017). IL-17F induces IL-6 via TAK1-NFκB pathway in airway smooth muscle cells. Immunity Inflammation and Disease, 5(2), 124-131. https://doi.org/10.1002/iid3.149