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Placenta-derived IL-32β activates neutrophils to promote preeclampsia development

查看全文 作  者:Dan [1]Liu;Qiang [2]Li;Hailin [1]Ding;Guangfeng [1]Zhao;Zhiyin [1]Wang;Chenrui [1]Cao;Yimin [1]Dai;Mingming [1]Zheng;Xiangyu [1]Zhu;Qianwen [1]Wu;Ya [1]Wang;Honglei [1]Duan;Huirong [1]Tang;Xianyan [1]Lu;Yayi [3]Hou;Yali [1,2]Hu 高影响力作者 机构地区:[1]Department of Obstetrics and Gynecology,The Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing,China;[2]Department of Obstetrics and Gynecology,Drum Tower Clinic Medical College of Nanjing Medical University,Nanjing,Jiangsu,China;[3]The State Key Laboratory of Pharmaceutical Biotechnology,Division of Immunology,Medical School,Nanjing University,Nanjing,China高影响力机构 出  处:《Cellular & Molecular Immunology》索引2021年第18卷第4期,共13页高影响力期刊 基  金:funded by grants from the National Key R&D Program of China(2018YFC1004404);National Natural Science Foundation of China(81701474 and 82071600);Jiangsu Provincial Key Medical Center(YXZXB2016004);China Postdoctoral Science Foundation(2019M651807);Key Research and Development Program of Jiangsu Province(BE2019706);Jiangsu Biobank of Clinical Resources(BM2015004);The Open Project of Jiangsu Biobank of Clinical Resources(SBK202006001);Maternal and Child Health Project in Jiangsu Province(F201742). 摘  要:Immune activation at the maternal-fetal interface is a main pathogenic factor of preeclampsia(PE).Neutrophils(PMNs)are activated in PE patients,but the mechanism and consequences of PMN activation need to be further explored.Here,we demonstrated that interleukin-32(IL-32)expression was significantly upregulated in syncytiotrophoblasts(STBs)and that IL-32β was the major isoform with increased expression in the placenta of severe PE(sPE)patients.Furthermore,the level of IL-32 expression in the placenta was correlated with its level in the serum of sPE patients,indicating that IL-32 in the serum is derived mainly from the placenta.Then,in vitro experiments showed that IL-32β could highly activate PMNs and that these IL-32β-activated PMNs were better able to adhere to endothelial cells(HUVECs)and enhance the expression of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)in HUVECs,which could be reversed by preincubation with the NADPH oxidase inhibitor VAS 2870.In addition,we showed that IL-32β mainly activated PMNs by binding to proteinase 3.Finally,IL-32β administration induced a PE-like phenotype in a pregnant mouse model.This study provides evidence of the involvement of IL-32β in the pathogenesis of PE. 关 键 词:IL-32 NEUTROPHIL PREECLAMPSIA ROS HUVEC
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