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Krüppel-like factor 4 regulates the expression of inducible nitric oxide synthase induced by TNF-α in human fibroblast-like synoviocyte MH7A cells

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Abstract

Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, has been implicated in the inflammation mediated by macrophages and endothelial cells by regulating the expression of inflammatory mediators. Here, we investigated whether KLF4 affects the expression of inducible nitric oxide synthase (iNOS), an important inflammatory mediator, in the human RA fibroblast-like synovial cell line MH7A. A pcDNA3.1-KLF4 plasmid or short interfering RNA KLF4 was transfected into MH7A cells, and the iNOS expression and nitric oxide (NO) production were analyzed by quantitative PCR, immunoblotting, and nitrite measurement. The iNOS promoter activity was determined by luciferase assay. The results showed overexpression of KLF4 increased iNOS expression and NO production in the presence or absence of TNF-α. Conversely, KLF4 knockdown markedly reduced iNOS expression and NO production induced by TNF-α. KLF4 activated the transcription activity of iNOS promoter in MH7A cells stimulated by TNF-α. This study indicates that KLF4 is important for regulating the expression of iNOS by TNF-α in human synoviocytes.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81373139), the Zhejiang Provincial Natural Science Foundation of China (LY16H100001), and the Zhejiang Provincial Medical Scientific Research Foundation (2015KYA206).

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Author notes

  1. Xuanrong Mo and Jie Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Basic Medical Sciences, School of Medicine of Taizhou University, Taizhou, 318000, Zhejiang, China

    Xuanrong Mo, Jie Chen, Xinjuan Wang, Zhenyu Pan, Yuping Ke, Zhidong Zhou & Xinjing Luo

  2. Department of Cardiology, Yingzhou District Second people’s Hospital, Ningbo, 315000, China

    Jiangwen Xie & Guoju Lv

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  1. Xuanrong Mo
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  2. Jie Chen
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Correspondence to Xinjing Luo.

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Mo, X., Chen, J., Wang, X. et al. Krüppel-like factor 4 regulates the expression of inducible nitric oxide synthase induced by TNF-α in human fibroblast-like synoviocyte MH7A cells. Mol Cell Biochem 438, 77–84 (2018). https://doi.org/10.1007/s11010-017-3115-9

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  • DOI: https://doi.org/10.1007/s11010-017-3115-9

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