Wang Yong-Jing, Xu Qiu-Yan, Ye Wei-Ming, Yi Dong-Yu, Zheng Xin-Qi, Xie Lin, Lin Li-Rong, Lin Yu, Yang Tian-Ci
Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China.
Guangyuan Hospital of Traditional Chinese Medicine, Guangyuan 628000, China.
ACS Infect Dis. 2023 Dec 8;9(12):2548-2559. doi: 10.1021/acsinfecdis.3c00401. Epub 2023 Nov 20.
M2 macrophages were related to local immune homeostasis and maternal-fetal tolerance in normal pregnancy; whether M2 macrophages can respond to the stimulation of to mediate placental vascular inflammation injury is unclear. In this study, M2 macrophages were constructed to investigate the impact of on macrophage polarization and the underlying signaling pathway involved in this process, and the influence of macrophage polarization triggered by on the apoptosis and angiogenesis of human umbilical vein endothelial cells (HUVEC) was also explored. The results showed that M2 macrophage markers (CD206 and PPARγ) and anti-inflammatory factors (TGFβ and CCL18) were decreased, while M1 macrophage marker CD80 and inflammatory cytokines (IL1β and TNFα) were increased when M2 macrophages were treated with , indicating that promoted the polarization of M2 subtype macrophages to the M1 subtype. Moreover, -induced M1 macrophage polarization was found to be significantly correlated with the activation of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 1 (STAT1). In addition, -induced M1 macrophages were found to promote apoptosis and inhibit the angiogenesis of HUVECs, and JAK1 or STAT1 inhibitors could weaken the apoptosis rate and promote the angiogenesis of HUVECs. These findings revealed that promoted the polarization of M2 macrophages to the M1 subtype through the JAK1-STAT1 signal pathway mediating the apoptosis and inhibiting angiogenesis of HUVECs, which may provide a possible mechanism for -induced adverse pregnancy outcomes.
M2巨噬细胞与正常妊娠中的局部免疫稳态和母胎耐受有关；M2巨噬细胞是否能对[未提及物质]的刺激作出反应以介导胎盘血管炎症损伤尚不清楚。在本研究中，构建M2巨噬细胞以研究[未提及物质]对巨噬细胞极化的影响以及该过程中涉及的潜在信号通路，同时还探讨了[未提及物质]触发的巨噬细胞极化对人脐静脉内皮细胞（HUVEC）凋亡和血管生成的影响。结果表明，用[未提及物质]处理M2巨噬细胞时，M2巨噬细胞标志物（CD206和PPARγ）和抗炎因子（TGFβ和CCL18）减少，而M1巨噬细胞标志物CD80和炎性细胞因子（IL1β和TNFα）增加，表明[未提及物质]促进了M2亚型巨噬细胞向M1亚型的极化。此外，发现[未提及物质]诱导的M1巨噬细胞极化与Janus激酶1（JAK1）和信号转导及转录激活因子1（STAT1）的激活显著相关。另外，发现[未提及物质]诱导的M1巨噬细胞促进HUVECs的凋亡并抑制其血管生成，而JAK1或STAT1抑制剂可减弱HUVECs的凋亡率并促进其血管生成。这些发现揭示，[未提及物质]通过JAK1-STAT1信号通路促进M2巨噬细胞向M1亚型极化，介导HUVECs的凋亡并抑制其血管生成，这可能为[未提及物质]诱导的不良妊娠结局提供一种可能的机制。
