PMID- 33995360
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20210920
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Stimulation of alpha7 Nicotinic Acetylcholine Receptor by Nicotine Suppresses 
      Decidual M1 Macrophage Polarization Against Inflammation in 
      Lipopolysaccharide-Induced Preeclampsia-Like Mouse Model.
PG  - 642071
LID - 10.3389/fimmu.2021.642071 [doi]
LID - 642071
AB  - Changes in decidual macrophage polarization affect local inflammatory 
      microenvironment and lead to adverse pregnancy outcomes. However, the regulatory 
      mechanism of macrophage polarization in preeclampsia (PE) remains unclear. In 
      this study, we found that alpha7nAChR expression was significantly down-regulated in 
      decidual macrophages in PE patients compared to normal pregnant women, 
      accompanied by a reduced proportion of M2 phenotype and an increased proportion 
      of M1 phenotype; these results suggested that the reduced alpha7nAChR activity might 
      contribute to changes in the polarization of decidual macrophages. Then, we 
      further investigated the regulatory role of alpha7nAChR activation by nicotine on 
      decidual macrophage polarization and placental remodeling in the PE-like mouse 
      model. The PE mice were obtained by i.p. injection of 10 microg/kg lipopolysaccharide 
      (LPS) gestational day (GD) 13, and 40 microg/kg LPS daily until GD16. Subcutaneous 
      injection of 1.0 mg/kg nicotine was administrated from GD14 to GD18. Nicotine 
      treatment increased the decreased M2 phenotype and inhibited the increased M1 
      phenotype in decidua of pregnant mice induced by LPS. The levels of 
      pro-inflammatory cytokines in decidua were higher but the levels of 
      anti-inflammatory cytokines were lower in PE mice compared to the controls, 
      nicotine reversed these changes. The level of choline acetyltransferase (CHAT) 
      was reduced in the LPS-treated group, it was increased following nicotine 
      treatment. Damage of spiral artery remodeling and down-regulation of markers 
      related to trophoblast invasion in placentas were found in PE mice; nicotine 
      improved these pathological structures of placentas. alpha-bungarotoxin (alpha-BGT) which 
      is specific antagonist for alpha7nAChR could abolish the effects of nicotine on 
      decidual macrophage polarization, trophoblast arrangement and vascular structure 
      in placental tissue in PE mice. These results suggest that alpha7nAChR plays an 
      important regulatory role in maternal-fetal inflammation and placental remodeling 
      in preeclampsia and may provide a theoretical basis for the discovery of new 
      strategies for preeclampsia.
CI  - Copyright (c) 2021 Han, Li, Li, Zheng, Lin, Zhou, Guo, He and Yang.
FAU - Han, Xinjia
AU  - Han X
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Li, Ping
AU  - Li P
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Zheng, Zheng
AU  - Zheng Z
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Lin, Baohua
AU  - Lin B
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Zhou, Bei
AU  - Zhou B
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Guo, Kaimin
AU  - Guo K
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - He, Ping
AU  - He P
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Yang, Jinying
AU  - Yang J
AD  - Department of Obstetrics, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210428
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cell Differentiation/immunology
MH  - Decidua/*immunology/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Inflammation/chemically induced/immunology
MH  - Lipopolysaccharides/toxicity
MH  - Macrophages/*immunology
MH  - Mice
MH  - Nicotine/pharmacology
MH  - Nicotinic Agonists/pharmacology
MH  - Pre-Eclampsia/immunology/*metabolism
MH  - Pregnancy
MH  - alpha7 Nicotinic Acetylcholine Receptor/*metabolism
PMC - PMC8113862
OTO - NOTNLM
OT  - decidual macrophage
OT  - nicotine
OT  - placenta
OT  - preeclampsia
OT  - alpha7nAChR
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest. The reviewer WW declared a shared affiliation with the 
      authors to the handling editor at the time of review.
EDAT- 2021/05/18 06:00
MHDA- 2021/09/21 06:00
PMCR- 2021/01/01
CRDT- 2021/05/17 06:04
PHST- 2020/12/15 00:00 [received]
PHST- 2021/03/30 00:00 [accepted]
PHST- 2021/05/17 06:04 [entrez]
PHST- 2021/05/18 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.642071 [doi]
PST - epublish
SO  - Front Immunol. 2021 Apr 28;12:642071. doi: 10.3389/fimmu.2021.642071. eCollection 
      2021.