HMGB1 release from trophoblasts contributes to inflammation during Brucella melitensis infection
HMGB1 release from trophoblasts contributes to inflammation during Brucella melitensis infection
复制标题
滋养层细胞释放 HMGB1 导致布鲁氏菌感染期间的炎症
DOI：
10.1111/cmi.13080
复制
发表时间：
2019-07-02
影响因子：
3.4
通讯作者：
Peng, Qisheng
中科院分区：
文献类型：
--
作者：
Liu, Xiaofeng;Zhou, Mi;Peng, Qisheng
布鲁氏菌感染可引起妊娠动物急性坏死性炎症；然而，导致胎盘炎的病理生理机制尚不清楚。本研究表明，高迁移率组框1 （HMGB1）在melitensis感染的妊娠小鼠模型中作为胎盘炎症的介质。在蜜蜂芽胞杆菌感染期间，滋养细胞和胎盘外植体中HMGB1水平升高。用中和抗体抑制HMGB1活性，可显著降低感染B. melitensis的滋养细胞或胎盘中炎症因子的分泌，而重组HMGB1 （rHMGB1）的管理增加了炎症反应。从机制上说，这种炎症反应的减少是由于HMGB1活性的抑制，这导致丝裂原活化蛋白激酶和活化B细胞的核因子kappa-轻链增强子（NF-kappa B）活化的抑制。此外，HMGB1的中和抗体可阻止B. melitensis感染诱导的滋养细胞中烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶的激活。相反，在体外用rHMGB1刺激滋养层细胞会激活NADPH氧化酶，增加ROS的产生，这导致滋养层细胞或胎盘内的细菌负担增加。在体内，抗hmgb1抗体治疗增加了布氏菌感染的妊娠小鼠胎盘内存活的数量，但成功地降低了胎盘炎和流产的严重程度。
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.