期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 14, 期 10, 页码 830-841出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2016.31
关键词
acute inflammation; BRD7; DSS; LPS; NF-kappa B pathway
类别
资金
- National Natural Science Foundation of China [81071686, 81328019, 81572748]
- Central South University [2015zzts097]
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-alpha (TNF-alpha), 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-kappa B; p65) and an increased NF-kappa B 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-alpha, p65, CXCL-1 and iNOS, and an increased level of NF-kappa B (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-kappa B signaling pathway, which provides evidence to aid in understanding the therapeutic effects of BRD7 on inflammatory diseases.
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