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BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway

Cellular & Molecular Immunology volume 14, pages 830–841 (2017)Cite this article

Abstract

Increasing evidence has shown a strong association between tumor-suppressor genes and inflammation. However, the role of BRD7 as a novel tumor suppressor in inflammation remains unknown. In this study, by observing BRD7 knockout mice for 6–12 months, we discovered that compared with BRD7+/+ mice, BRD7−/− mice were more prone to inflammation, such as external inflammation and abdominal abscess. By using mouse embryo fibroblast (MEF) cells from the BRD7 knockout mouse, an in vitro lipopolysaccharide (LPS)-stimulated MEF cell line was established. The mRNA levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), chemokine (C-X-C motif) ligand 1 (CXCL-1) and inducible nitric oxide synthase (iNOS) were significantly increased in BRD7−/− MEF cells compared with BRD7+/+ MEF cells after LPS stimulation for 1 or 6 h. In addition, the cytoplasm-to-nucleus translocation of nuclear factor kappa-B (NF-κB; p65) and an increased NF-κB reporter activity were observed in BRD7−/− MEF cells at the 1 h time point but not at the 6 h time point. Furthermore, an in vivo dextran sodium sulfate (DSS)-induced acute colitis model was created. As expected, the disease activity index (DAI) value was significantly increased in the BRD7−/− mice after DSS treatment for 1–5 days, which was demonstrated by the presence of a significantly shorter colon, splenomegaly and tissue damage. Moreover, higher expression levels of IL-6, TNF-α, p65, CXCL-1 and iNOS, and an increased level of NF-κB (p65) nuclear translocation were also found in the DSS-treated BRD7−/− mice. These findings suggest that BRD7 has an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway, which provides evidence to aid in understanding the therapeutic effects of BRD7 on inflammatory diseases.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (grant nos 81071686, 81328019 and 81572748) and the Free Exploration Program of Central South University (grant no. 2015zzts097). We thank the Shanghai Research Center for Biomodel Organisms (Shanghai, China) for their excellent technical assistance in generating the BRD7−/− mice.

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Authors and Affiliations

  1. Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Ran Zhao, Yuanzheng Qiu & Ming Zhou

  2. Cancer Research Institute, Central South University, Changsha, 410078, Hunan, China

    Ran Zhao, Yukun Liu, Heran Wang, Jing Yang, Weihong Niu, Wei Xiong, Jian Ma, Xiaoling Li, Guiyuan Li & Ming Zhou

  3. Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, Hunan, China

    Ran Zhao, Yukun Liu, Heran Wang, Jing Yang, Weihong Niu, Wei Xiong, Jian Ma, Xiaoling Li, Guiyuan Li & Ming Zhou

  4. The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Songqing Fan

  5. Mitchell Cancer Institute, University of South Alabama, Mobile, 36604, AL, USA

    Joshua B Phillips & Ming Tan

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  1. Ran Zhao
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Zhao, R., Liu, Y., Wang, H. et al. BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway. Cell Mol Immunol 14, 830–841 (2017). https://doi.org/10.1038/cmi.2016.31

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