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

作　　者：Ran Zhao Yukun Liu Heran Wang Jing Yang Weihong Niu Songqing Fan Wei Xiong Jian Ma Xiaoling Li Joshua B Phillips Ming Tan Yuanzheng Qiu Guiyuan Li Ming Zhou 

机构地区：[1]Xiangya Hospital,Central South University,Changsha,Hunan 410008,China [2]Cancer Research Institute,Central South University,Changsha,Hunan 410078,China [3]Key Laboratory of Carcinogenesis and Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion,Ministry of Education,Changsha,Hunan 410078,China [4]The Second Xiangya Hospital,Central South University,Changsha,Hunan 410011,China [5]Mitchell Cancer Institute,University of South Alabama,Mobile,AL 36604,USA

出　　处：《Cellular & Molecular Immunology》2017年第10期830-841,共12页中国免疫学杂志（英文版）

基　　金：by grants from the National Natural Science Foundation of China(grant nos 81071686,81328019 and 81572748);the Free Exploration Program of Central South University(grant no.2015zzts097).

摘　　要：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.

关 键 词：acute inflammation BRD7 DSS LPS NF-κB pathway 

分 类 号：R73[医药卫生—肿瘤]