title: BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway.
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.
authors.affiliation: Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.|Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Heran
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Niu
authors.affiliation: The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Songqing
authors.initials: S
authors.lastname: Fan
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Phillips
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.affiliation: Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.|Cancer Research Institute, Central South University, Changsha, Hunan 410078, China.|Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan 410078, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D016264:Dextran Sulfate; D005347:Fibroblasts / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
chemical_list: D054360:Chemokine CXCL1; D002868:Chromosomal Proteins, Non-Histone; D016264:Dextran Sulfate; D015850:Interleukin-6; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C400206:Brd7 protein, mouse; D000092468:Bromodomain Containing Proteins; C475895:Cxcl1 protein, mouse; C498144:Rela protein, mouse; C496317:Nos2 protein, mouse