探索人早孕绒毛组织和滋养细胞中白细胞介素25(interleukin 25,IL-25)及其受体的表达,以及IL-25对滋养细胞的促增殖作用。免疫组织化学法检测IL-25在正常早孕期绒毛组织的表达;流式细胞术检测IL-25及其受体在正常妊娠和自然流产绒毛组织的滋养细胞中的表达;CCK-8实验分析重组IL-25(rhIL-25)及其中和性抗体对人绒毛膜滋养细胞株HTR-8/SVneo细胞活力的影响。结果显示IL-25在正常绒毛组织滋养细胞中呈阳性表达,自然流产患者绒毛滋养细胞的IL-25及其受体的表达均低于正常妊娠(P〈0.001);重组IL-25处理后,HTR-8/SVneo细胞活力以时间依赖和剂量依赖方式显著增强(P〈0.001或P〈0.000 1);相反,IL-25中和性抗体明显抑制其细胞活力(P〈0.05或P〈0.01或P〈0.001)。结果表明人早孕母-胎界面滋养细胞表达IL-25,以自分泌方式促进自身增殖,IL-25异常低表达可能参与反复自然流产的发病机制。
We aimed to explore the expressions of IL-25 and its receptor in chorionic villi and trophoblastic cells during early pregnancy as well as the influence of IL-25 on the viability of trophoblastic cells.The expressions of IL-25 and its receptor in chorionic villi and trophoblastic cells from women with normal pregnancy and patients with recurrent spontaneous abortion were detected by IHC and flow cytometry.Then,the proliferation of HTR-8/SVneo cells treated with rhIL-25 and its neutralizing antibody was analyzed by CCK-8assay.We found that IL-25 was positively expressed in trophoblast cells of villi from women with normal pregnancy.The expressions of IL-25 and its receptor in trophoblastic cells of recurrent spontaneous abortion patients were significantly lower than those of the normal pregnancy(P 〈0.001).Treatment with recombinant IL-25 significantly increased the viability of HTR-8/SVneo cells in a time-dependent and dose-dependent manner(P 〈0.001 or P 〈0.000 1);on the contrary,IL-25 neutralizing antibody notably inhibited the proliferation and viability of HTR-8/SVneo cells(P 〈0.05,P 〈 0.01 or P 〈 0.001).In conclusion,trophoblast cells-derived IL-25 promotes self-proliferation,and the abnormally low level of IL-25 may participate in the pathogenesis of recurrent spontaneous abortion.