Ye Aihua, Li Liling, Chen Haozhong, Tao Ping, Lou Shuiping
Department of Obstetrics and Gynecology, The Maternal and Child Health Hospital of Longhua District, Shenzhen, Guangdong, 518109, China.
Department of Obstetrics, The Maternal and Child Health Hospital of Longhua District, Shenzhen, Guangdong, 518109, China.
Placenta. 2024 Mar 6;147:42-51. doi: 10.1016/j.placenta.2024.01.014. Epub 2024 Jan 29.
Preterm birth (PTB) frequently results from the syndrome of preterm labor (PTL). PTL is linked to an atypical maternal inflammatory response, as well as intrauterine inflammation and/or infection. In this study, we explored the mechanisms involved in nicotine-mediated abnormal macrophage polarization and trophoblast invasion associated with PTL.
First, THP-1-M0 macrophages were generated by treating the human monocytic leukemia cell line (THP-1) with phorbol 12-myristate 13-acetate for a duration of 24 h. Afterward, nicotine treatment was administered, followed by coculturing with the HTR-8/SVneo trophoblast cell line (HTR-8) at a ratio of 1:1. Next, we transfected sh-α7nAChR and treated THP-1-M0 macrophages and HTR-8 cells with nicotine. In addition, we transfected THP-1-M0 macrophages with sh-NC or sh-SIRT1 or subjected them to 4 nM nicotinamide adenine dinucleotide (NAD) metabolic inhibitor FK866 treatment. Moreover, HTR-8 cells were treated with nicotine, after which THP-1-M0 macrophages were cocultured with HTR-8 cells. Finally, we constructed an in vivo RU486-induced PTL rat model to verify the effect of nicotine and the mechanisms involved.
We found that nicotine affected polarization and α7nAChR expression in HTR-8 cocultured THP-1-M0 macrophages. Knocking down α7nAChR blocked the effect of nicotine on the proliferation and invasion of HTR-8 cells. Furthermore, nicotine activated the α7nAChR/SIRT1 axis to regulate THP-1-M0 macrophage polarization through the cholinergic anti-inflammatory pathway. Additionally, NAD metabolism mediated the role of the α7nAChR/SIRT1 axis in nicotine-induced polarization of HTR-8 cocultured THP-1-M0 macrophages. In vivo experiments demonstrated that nicotine alleviated inflammation in PTL rats, which involved the α7nAChR/SIRT1 axis.
Nicotine regulated abnormal macrophage polarization and trophoblast invasion associated with PTL via the α7nAChR/SIRT1 axis.
早产（PTB）常由早产综合征（PTL）导致。PTL与非典型母体炎症反应以及宫内炎症和/或感染有关。在本研究中，我们探讨了尼古丁介导的与PTL相关的异常巨噬细胞极化和滋养层细胞侵袭的机制。
首先，用佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯处理人单核细胞白血病细胞系（THP - 1）24小时，以生成THP - 1 - M0巨噬细胞。之后，给予尼古丁处理，然后以1:1的比例与HTR - 8/SVneo滋养层细胞系（HTR - 8）共培养。接下来，我们转染sh - α7nAChR并用尼古丁处理THP - 1 - M0巨噬细胞和HTR - 8细胞。此外，我们用sh - NC或sh - SIRT1转染THP - 1 - M0巨噬细胞，或用4 nM烟酰胺腺嘌呤二核苷酸（NAD）代谢抑制剂FK866处理它们。而且，用尼古丁处理HTR - 8细胞，之后将THP - 1 - M0巨噬细胞与HTR - 8细胞共培养。最后，我们构建了体内RU486诱导的PTL大鼠模型，以验证尼古丁的作用及其涉及的机制。
我们发现尼古丁影响与HTR - 8共培养的THP - 1 - M0巨噬细胞的极化和α7nAChR表达。敲低α7nAChR可阻断尼古丁对HTR - 8细胞增殖和侵袭的影响。此外，尼古丁激活α7nAChR/SIRT1轴，通过胆碱能抗炎途径调节THP - 1 - M0巨噬细胞极化。另外，NAD代谢介导α7nAChR/SIRT1轴在尼古丁诱导的与HTR - 8共培养的THP - 1 - M0巨噬细胞极化中的作用。体内实验表明，尼古丁减轻了PTL大鼠的炎症，这涉及α7nAChR/SIRT1轴。
尼古丁通过α7nAChR/SIRT1轴调节与PTL相关的异常巨噬细胞极化和滋养层细胞侵袭。
