Chai Xiaoshan, Wu Xianqing, He Ling, Ding Hui
Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
Exp Ther Med. 2021 Sep;22(3):1003. doi: 10.3892/etm.2021.10436. Epub 2021 Jul 15.
Macrophage-induced inflammation is a major factor in the pathogenesis of endometriosis. The underlying mechanisms, however, remain largely unknown. TNF-α, IL-6, IL-10 and C-C motif chemokine 20 (CCL20) levels in endometrial extracts were determined using Luminex cytokine kits. Additionally, protein arginine methyltransferase 5 (PRMT5) levels were measured using reverse transcription-quantitative PCR and western blotting. IL-6 and IP-10 levels in cells were measured using ELISA kits. In the present study, it was revealed that PRMT5 expression at both the mRNA and protein levels in THP-1-derived macrophages was significantly decreased following treatment with serum or extracts of endometrium from patients with endometriosis in the presence of lipopolysaccharide, compared with that in control cells, suggesting a possible role for macrophage-derived PRMT5 in mediating the interaction between macrophages and endometrium in endometriosis. Mechanistically, macrophage PRMT5 expression was regulated in an NF-κB-dependent and Smad2/3-independent manner, indicating that PRMT5 is a downstream target of NF-κB. Importantly, macrophage-derived PRMT5 was required for macrophage activation in endometriosis, as evidenced by the PRMT5-dependent secretion of IL-6 and IFN-γ-induced protein 10 from THP-1-derived macrophages. The present study identified NF-κB-dependent PRMT5 as a novel regulator of macrophage activation in endometriosis. Targeting PRMT5 in macrophages may be a potential therapeutic strategy against endometriosis.
巨噬细胞诱导的炎症是子宫内膜异位症发病机制中的一个主要因素。然而，其潜在机制在很大程度上仍不清楚。使用Luminex细胞因子检测试剂盒测定子宫内膜提取物中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和C-C基序趋化因子20（CCL20）的水平。此外，使用逆转录定量聚合酶链反应和蛋白质印迹法测量蛋白质精氨酸甲基转移酶5（PRMT5）的水平。使用酶联免疫吸附测定试剂盒测量细胞中IL-6和干扰素γ诱导蛋白10（IP-10）的水平。在本研究中，发现与对照细胞相比，在用脂多糖处理的情况下，来自子宫内膜异位症患者的血清或子宫内膜提取物处理后，THP-1来源的巨噬细胞中PRMT5在mRNA和蛋白质水平的表达均显著降低，这表明巨噬细胞来源的PRMT5可能在介导子宫内膜异位症中巨噬细胞与子宫内膜之间的相互作用中发挥作用。从机制上讲，巨噬细胞PRMT5的表达是以核因子κB（NF-κB）依赖性和Smad2/3非依赖性方式调节的，这表明PRMT5是NF-κB的下游靶点。重要的是，巨噬细胞来源的PRMT5是子宫内膜异位症中巨噬细胞激活所必需的，THP-1来源的巨噬细胞中IL-6和IFN-γ诱导蛋白10的PRMT5依赖性分泌证明了这一点。本研究确定NF-κB依赖性PRMT5是子宫内膜异位症中巨噬细胞激活的一种新型调节因子。靶向巨噬细胞中的PRMT5可能是一种针对子宫内膜异位症的潜在治疗策略。
