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

被引:17
|
作者
Nakajima, Masayuki [1 ]
Kawaguchi, Mio [1 ]
Ota, Kyoko [1 ]
Fujita, Junichi [1 ]
Matsukura, Satoshi [2 ]
Huang, Shau-Ku [3 ,4 ]
Morishima, Yuko [1 ]
Ishii, Yukio [1 ]
Satoh, Hiroaki [1 ]
Sakamoto, Tohru [1 ]
Hizawa, Nobuyuki [1 ]
机构
[1] Univ Tsukuba, Fac Med, Dept Pulm Med, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan
[2] Showa Univ, Resp Dis Ctr, Northern Yokohama Hosp, Yokohama, Kanagawa, Japan
[3] Johns Hopkins Univ, Ctr Asthma & Allergy, Baltimore, MD 21224 USA
[4] Natl Hlth Res Inst, Taipei, Taiwan
关键词
IL-17F; NF-kappa B; TAK1; KAPPA-B ACTIVATION; T-CELLS; EPITHELIAL-CELLS; IN-VIVO; ASTHMA; CYTOKINE; INTERLEUKIN-17F; TAK1; IDENTIFICATION; INDUCTION;
D O I
10.1002/iid3.149
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 -activated kinase 1 (TAK1) and nuclear factor (NF)-kappa B 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-kappa B was detected by Western blotting. The effect of TAK1 inhibitor 5Z-7-oxozeaenol and NF-kappa B 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-kappa B, 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-kappa B 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.
引用
收藏
页码:124 / 131
页数:8
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