Xie Qi, He Hua, Wu Ya-Hong, Zou Lu-Jie, She Xiao-Ling, Xia Xiao-Meng, Wu Xian-Qing
Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, China.
J Obstet Gynaecol Res. 2019 May;45(5):1045-1057. doi: 10.1111/jog.13938. Epub 2019 Mar 6.
This study aimed to investigate the in vitro alterations of the expression of signal regulatory protein-α (SIRP-α) and CD36 in macrophages in the endometriosis condition.
The expression of SIRP-α and CD36 was measured in peritoneal macrophages and peripheral blood mononuclear cells of endometriosis patients and control participants. The expressions of SIRP-α and CD36 were measured in human acute monocytic leukemia (THP-1) cell-derived macrophages that were treated with interleukin-6 (IL-6)-induced conditioned medium, eutopic versus normal endometrial homogenate, or lipopolysaccharide in the presence or absence of nuclear factor kappa-B (NF-κB) or transforming growth factor (TGF-β) inhibitors, respectively.
Peritoneal macrophages that were isolated from women with endometriosis exhibited an enhanced expression of SIRP-α and a decreased expression of CD36 compared to control participants. Women with endometriosis had significantly higher levels of SIRP-α and CD36 in peripheral circulating mononuclear cells than in control participants. SIRP-α expression was significantly increased, whereas the CD36 expression was decreased in THP-1 cell-derived macrophages after treatment with eutopic endometrial homogenate. Intervention with IL-6-induced conditioned medium resulted in the downregulation of SIRP-α but the upregulation of CD36 in THP-1 cells. Incubation with the NF-κBp50 inhibitor decreased the expression of CD36 and SIRP-α in macrophages that were treated with normal endometrial homogenate, whereas the TGF-β inhibitor enhanced the CD36 expression of THP-1 cell-derived macrophages treated with eutopic endometrial homogenate.
The eutopic endometrium could reduce the phagocytic ability of peritoneal macrophages in women with endometriosis through the modulation of SIRP-α and CD36 expression. Inhibition of the TGF-β signal pathway may be a potential therapeutic target for the treatment of endometriosis.
本研究旨在调查子宫内膜异位症状态下巨噬细胞中信号调节蛋白α（SIRP-α）和CD36表达的体外变化。
测量子宫内膜异位症患者和对照参与者的腹膜巨噬细胞和外周血单核细胞中SIRP-α和CD36的表达。分别在存在或不存在核因子κB（NF-κB）或转化生长因子（TGF-β）抑制剂的情况下，测量用白细胞介素-6（IL-6）诱导的条件培养基、在位内膜与正常子宫内膜匀浆或脂多糖处理的人急性单核细胞白血病（THP-1）细胞衍生的巨噬细胞中SIRP-α和CD36的表达。
与对照参与者相比，从子宫内膜异位症女性中分离出的腹膜巨噬细胞表现出SIRP-α表达增强和CD36表达降低。子宫内膜异位症女性外周循环单核细胞中SIRP-α和CD36的水平明显高于对照参与者。在用在位子宫内膜匀浆处理后，THP-1细胞衍生的巨噬细胞中SIRP-α表达显著增加，而CD36表达降低。用IL-6诱导的条件培养基干预导致THP-1细胞中SIRP-α下调但CD36上调。用NF-κBp50抑制剂孵育可降低用正常子宫内膜匀浆处理的巨噬细胞中CD36和SIRP-α的表达，而TGF-β抑制剂可增强用在位子宫内膜匀浆处理的THP-1细胞衍生的巨噬细胞的CD36表达。
在位内膜可通过调节SIRP-α和CD36的表达降低子宫内膜异位症女性腹膜巨噬细胞的吞噬能力。抑制TGF-β信号通路可能是治疗子宫内膜异位症的潜在治疗靶点。
