Stimulation of α7 Nicotinic Acetylcholine Receptor by Nicotine Suppresses Decidual M1 Macrophage Polarization Against Inflammation in Lipopolysaccharide-Induced Preeclampsia-Like Mouse Model.
Stimulation of α7 Nicotinic Acetylcholine Receptor by Nicotine Suppresses Decidual M1 Macrophage Polarization Against Inflammation in Lipopolysaccharide-Induced Preeclampsia-Like Mouse Model.
复制标题
尼古丁刺激 α7 烟碱乙酰胆碱受体抑制脂多糖诱导的先兆子痫样小鼠模型中蜕膜 M1 巨噬细胞的抗炎症极化
DOI：
10.3389/fimmu.2021.642071
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Han X;Li W;Li P;Zheng Z;Lin B;Zhou B;Guo K;He P;Yang J
蜕膜巨噬细胞极化的变化影响局部炎症微环境并导致不良妊娠结局。然而，先兆子痫（PE）中巨噬细胞极化的调节机制仍不清楚。本研究发现，与正常孕妇相比，PE患者蜕膜巨噬细胞中α7nAChR表达显着下调，并伴有M2表型比例减少和M1表型比例增加；这些结果表明，α7nAChR 活性的降低可能导致蜕膜巨噬细胞极化的变化。然后，我们进一步研究了尼古丁激活α7nAChR对类PE小鼠模型中蜕膜巨噬细胞极化和胎盘重塑的调节作用。 PE小鼠是通过腹腔注射获得的。在妊娠第 13 天注射 10 µg/kg 脂多糖 (LPS)，并每天注射 40 µg/kg LPS，直至 GD16。 GD14至GD18皮下注射1.0mg/kg尼古丁。尼古丁处理增加了LPS诱导的妊娠小鼠蜕膜中M2表型的减少并抑制了M1表型的增加。与对照组相比，PE小鼠蜕膜中促炎细胞因子的水平较高，但抗炎细胞因子的水平较低，尼古丁逆转了这些变化。 LPS 治疗组的胆碱乙酰转移酶 (CHAT) 水平降低，尼古丁治疗后则升高。在PE小鼠中发现了螺旋动脉重塑的损伤和胎盘滋养层侵袭相关标志物的下调；尼古丁改善了胎盘的这些病理结构。 α-银环蛇毒素(α-BGT)是α7nAChR的特异性拮抗剂，可以消除尼古丁对PE小鼠蜕膜巨噬细胞极化、滋养层排列和胎盘组织血管结构的影响。这些结果提示α7nAChR在子痫前期母胎炎症和胎盘重塑中发挥重要的调节作用，可能为子痫前期新策略的发现提供理论依据。
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 α7nAChR 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 α7nAChR activity might contribute to changes in the polarization of decidual macrophages. Then, we further investigated the regulatory role of α7nAChR 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 µg/kg lipopolysaccharide (LPS) gestational day (GD) 13, and 40 µg/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. α-bungarotoxin (α-BGT) which is specific antagonist for α7nAChR 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 α7nAChR 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.
登录
查看更多内容
DOI：
10.1038/nrneph.2014.102
发表时间：
2014-08
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Chaiworapongsa T;Chaemsaithong P;Yeo L;Romero R
通讯作者：
Romero R
影响因子：
3.6
作者：
DaSilva-Arnold, Sonia C.;Zamudio, Stacy;Illsley, Nicholas P.
通讯作者：
Illsley, Nicholas P.
影响因子：
9.3
作者：
De Simone R;Ajmone-Cat MA;Carnevale D;Minghetti L
通讯作者：
Minghetti L
影响因子：
2.3
作者：
Brown, LM;Lacey, HA;Crocker, IP
通讯作者：
Crocker, IP
DOI：
10.1073/pnas.1706546114
发表时间：
2017-10-03
影响因子：
11.1
作者：
Garrido-Gomez, Tamara;Dominguez, Francisco;Simon, Carlos
通讯作者：
Simon, Carlos