Placenta-derived IL-32β Activates Neutrophils to Promote Preeclampsia Development

Overview

Journal Cell Mol Immunol

Date 2021 Mar 12

PMID 33707686

Citations 10

Authors

Dan Liu

Qiang Li

Hailin Ding

Guangfeng Zhao

Zhiyin Wang

Chenrui Cao

Yimin Dai

Mingming Zheng

Xiangyu Zhu

Qianwen Wu

Ya Wang

Honglei Duan

Huirong Tang

Xianyan Lu

Yayi Hou

Yali Hu

Affiliations

Soon will be listed here.

Abstract

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.

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