PMID- 34598084 OWN - NLM STAT- MEDLINE DCOM- 20220304 LR - 20220304 IS - 1532-3102 (Electronic) IS - 0143-4004 (Linking) VI - 115 DP - 2021 Nov TI - TREM-1 amplifies trophoblastic inflammation via activating NF-kappaB pathway during preeclampsia. PG - 97-105 LID - S0143-4004(21)00603-2 [pii] LID - 10.1016/j.placenta.2021.09.016 [doi] AB - INTRODUCTION: Excessive activation of maternal systemic inflammation is one of the underlying causes of pathology during the disease course of preeclampsia (PE). The triggering receptor expressed on myeloid cells-1 (TREM-1) participates in the development and persistence of inflammation. We hypothesized that dysregulated TREM-1 may be involved in the pathogenesis of PE by promoting the secretion of trophoblastic pro-inflammatory cytokines that augment inflammation. METHODS: The localization of TREM-1 in placenta and the extravillous trophoblast cell line (TEV-1) was determined by immunohistochemical staining. The expression level of TREM-1 and pro-inflammatory cytokines in placentas were compared between normal pregnancies and PE. We used lipopolysaccharide (LPS) to simulate trophoblastic inflammation. TEV-1 cells were transfected with TREM-1 plasmid and si-TREM-1 respectively, and then were incubated with LPS. The expression levels of pro-inflammatory cytokines and key molecules featured in nuclear transcription factor-kappaB (NF-kappaB) pathway were detected. Transwell assays were used to detect the effects of TREM-1 on cell migration and invasion. RESULTS: TREM-1 was localized on both villous trophoblasts (VTs) and extravillous trophoblasts (EVTs). TREM-1 and pro-inflammatory cytokines were up-regulated in preeclamptic placenta. Overexpression of TREM-1 promoted the activation of NF-kappaB pathway and the release of pro-inflammatory factors induced by LPS, and enhanced migration and invasion of TEV-1 cells. Inhibition of TREM-1 significantly attenuated LPS-induced effects and suppressed migration and invasion. DISCUSSION: This study suggested that TREM-1 was up-regulated in PE, and may promote the production of downstream inflammatory factors by activating NF-kappaB pathway in trophoblastic cells, thus exerting pro-inflammatory effects in the pathogenesis of PE. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Xie, Yin AU - Xie Y AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Li, Xuanxuan AU - Li X AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Lv, Dan AU - Lv D AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - He, Mengzhou AU - He M AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Sun, Yanan AU - Sun Y AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Lin, Xingguang AU - Lin X AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Fan, Yao AU - Fan Y AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Yang, Meitao AU - Yang M AD - Department of Gynecology and Obstetrics, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China. FAU - Xu, Heze AU - Xu H AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Zhang, Xiaolei AU - Zhang X AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Zhang, Yanling AU - Zhang Y AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Beejadhursing, Rajluxmee AU - Beejadhursing R AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Li, Fanfan AU - Li F AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. FAU - Deng, Dongrui AU - Deng D AD - Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: tjdengdongrui@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210924 PL - Netherlands TA - Placenta JT - Placenta JID - 8006349 RN - 0 (Interleukins) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (TREM1 protein, human) RN - 0 (Triggering Receptor Expressed on Myeloid Cells-1) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Cell Line, Transformed MH - Female MH - Humans MH - Inflammation/*physiopathology MH - Interleukins/genetics MH - Lipopolysaccharides/pharmacology MH - NF-kappa B/*physiology MH - Placenta/chemistry MH - Pre-Eclampsia/*physiopathology MH - Pregnancy MH - RNA, Messenger/analysis MH - Transfection MH - Triggering Receptor Expressed on Myeloid Cells-1/analysis/genetics/*physiology MH - Trophoblasts/chemistry/drug effects/*physiology MH - Tumor Necrosis Factor-alpha/genetics OTO - NOTNLM OT - Placenta OT - Preeclampsia OT - TREM-1 OT - Trophoblastic inflammation EDAT- 2021/10/02 06:00 MHDA- 2022/03/05 06:00 CRDT- 2021/10/01 20:31 PHST- 2021/04/22 00:00 [received] PHST- 2021/09/12 00:00 [revised] PHST- 2021/09/22 00:00 [accepted] PHST- 2021/10/02 06:00 [pubmed] PHST- 2022/03/05 06:00 [medline] PHST- 2021/10/01 20:31 [entrez] AID - S0143-4004(21)00603-2 [pii] AID - 10.1016/j.placenta.2021.09.016 [doi] PST - ppublish SO - Placenta. 2021 Nov;115:97-105. doi: 10.1016/j.placenta.2021.09.016. Epub 2021 Sep 24.