NF-κB mediated chemokines and cytokines regulate of uterine NK cell function in decidual tissue
Objective To investigate the role of nuclear factor κB(NF-κB)in mediating the regulation of chemokine and cytokine production during human endometrial stromal cell(hESC)decidualization,thus affecting the function of uterine natural killer cell(uNK).Methods 20 healthy pregnant women who underwent artificial abortion to terminate pregnancy at Department of Gynecology and Obstetrics,Tangdu Hospital,Air Force Medical University from October 1,2022 to March 1,2023 were selected.Their decidual tissues were collected,and pure human uNK cells were isolated.The hESC were transfected with siRel A to inhibit NF-κB activity,followed by in vitro decidualization induction.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect mRNA levels of relevant chemokines and cytokines.After inducing decidualization of siRel A-transfected hESC,they were co-cultured with primary human uNK cells,and uNK cells and cell supernatants were harvested separately.Flow cytometry was used to detect the cytokine secretion function of uNK.The supernatant of uNK was used for vitro tube formation assay,invasion assay and scratch assay to investigate the function of adjusting angiogenesis and trophoblast cells invasion and migration ability.Results Transfection with siRel A significantly decreased the mRNA expression levels of interferon-γ(IFN-γ),matrix metalloproteinase(MMP)9,and chemokine CCL2 in decidual stromal cells(DSC)induced by decidualization(t=3.290,6.415 and 5.095,respectively,P＜0.05).Inhibiting NF-κB activity and inducing decidualization of DSC suppressed the secretion of uNK-related factors vascular endothelial growth factor(VEGF),placentail growth factor(PLGF),and IFN-y after co-culture with uNK cells(t=6.641,7.743 and 8.886,respectively,P＜0.05).The ability of uNK cell supernatants to promote angiogenesis was impaired after co-culture(t=4.629 and 5.522,P＜0.05),and trophoblast invasion and migration were significantly reduced(t=8.329 and 7.190,P＜0.05).Conclusion NF-κB regulates the expression of chemokines and cytokines in DSC,thus influencing the function of uNK.
国家科技期刊平台
NSTL
万方数据
