文献类型：期刊文献

英文题名：HMGB1 release from trophoblasts contributes to inflammation during Brucella melitensis infection

作者：Liu, Xiaofeng[2];Zhou, Mi[3];Wu, Jing[4];Wang, Jun[5];Peng, Qisheng[1]

第一作者：Liu, Xiaofeng

通信作者：Peng, QS[1]

机构：[1]Jilin Univ, Inst Zoonosis, Minist Educ, Key Lab Zoonosis, Changchun 130062, Jilin, Peoples R China;[2]Tumor Hosp Jilin Prov, Clin Lab, Changchun, Jilin, Peoples R China;[3]Changchun Med Coll, Dept Microbiol, Changchun, Jilin, Peoples R China;[4]Gansu Univ Chinese Med, Sch Nursing, Lanzhou, Gansu, Peoples R China;[5]Shenzhen Ctr Chron Dis Control, Lab Dept, Shenzhen, Peoples R China

第一机构：Jilin Univ, Inst Zoonosis, Minist Educ, Key Lab Zoonosis, Changchun 130062, Jilin, Peoples R China

通信机构：[1]corresponding author), Jilin Univ, Inst Zoonosis, Minist Educ, Key Lab Zoonosis, Changchun 130062, Jilin, Peoples R China.

年份：2019

卷号：21

期号：10

外文期刊名：CELLULAR MICROBIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000476848800001)】；

基金：Fundamental Research Funds for the Central Universities; Natural Science Foundation of China, Grant/Award Numbers: 31372409 and 31870121

语种：英文

外文关键词：Brucella; HMGB1; inflammatory response; placentitis; trophoblast

摘要：Brucella melitensis infection causes acute necrotizing inflammation in pregnant animals; however, the pathophysiological mechanisms leading to placentitis are unknown. Here, we demonstrate that high-mobility group box 1 (HMGB1) acts as a mediator of placenta inflammation in B. melitensis-infected pregnant mice model. HMGB1 levels were increased in trophoblasts or placental explant during B. melitensis infection. Inhibition of HMGB1 activity with neutralising antibody significantly reduced the secretion of inflammatory cytokines in B. melitensis-infected trophoblasts or placenta, whereas administration of recombinant HMGB1 (rHMGB1) increased the inflammatory response. Mechanistically, this decreased inflammatory response results from inhibition of HMGB1 activity, which cause the suppression of both mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) activation. Moreover, neutralising antibody to HMGB1 prevented B. melitensis infection-induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in trophoblasts. In contrast, in vitro stimulation of trophoblasts with rHMGB1 caused activation of NADPH oxidase and increased the production of ROS, which contributes to high bacterial burden within trophoblasts or placenta. In vivo, treatment with anti-HMGB1 antibody increases the number of Brucella survival within placenta in B. melitensis-infected pregnant mice but successfully reduced the severity of placentitis and abortion.