The uterus in early pregnancy is a non-lymphoid organ that is enriched in natural killer （NK） cells. Studies to address the role of these abundant human NK cells at the maternal/fetal interface have focused on their...The uterus in early pregnancy is a non-lymphoid organ that is enriched in natural killer （NK） cells. Studies to address the role of these abundant human NK cells at the maternal/fetal interface have focused on their response to the major histocompatibility complex （MHC） molecules on fetal trophoblast cells that they contact. The interaction of maternal NK cell receptors belonging to the killer cell immunoglobulin-like receptor （KIR） family with trophoblast MHC class I molecules in pregnancy can regulate NK cell activation for secretion of pro-angiogenic factors that promote placental development. This review will cover the role of KIR at the maternal/fetal interface and focus on KIR2DL4, a KIR family member that is uniquely poised to play a role in pregnancy due to the restricted expression of its ligand, human leukocyte antigen （HLA）-G, by fetal trophoblast cells early in pregnancy. The pathways by which KIR2DL4-HLA-G interactions induce the cellular senescence of NK cells and the role of the resulting senescence-associated secretory phenotype （SASP） in vascular remodeling will be discussed in the context of reproduction.展开更多
目的探讨炎症因子白介素-1β(interleukin-1β,IL-1β)对软骨表层细胞(articular cartilage superficial zone cells,ACSCs)衰老的调控作用和相关机制。方法用纤连蛋白黏附法分离培养ACSCs,根据实验分为对照组和IL-1β处理组,采用MTT检...目的探讨炎症因子白介素-1β(interleukin-1β,IL-1β)对软骨表层细胞(articular cartilage superficial zone cells,ACSCs)衰老的调控作用和相关机制。方法用纤连蛋白黏附法分离培养ACSCs,根据实验分为对照组和IL-1β处理组,采用MTT检测细胞增殖情况,衰老相关-β-半乳糖苷酶(SA-β-gal)染色检测SA-β-gal阳性细胞数,Western blot检测p21和p53蛋白水平,实时荧光定量PCR(RT-qPCR)检测衰老相关分泌表型(senescence-associated secretory phenotype,SASP)因子il-6、Mmp-3和Mmp-13 m RNA水平,CellROX试剂检测活性氧(reactive oxygen species,ROS)水平,JC-1试剂检测线粒体膜电位。最后,取ACSCs设IL-1β处理组和IL-1β+N-乙酰半胱氨酸(N-acetylcysteine,NAC)处理组,检测NAC处理后对IL-1β引起的细胞ROS水平、细胞增殖、SA-β-gal阳性细胞数、p21和p53蛋白水平和SASP分泌因子水平的影响。结果IL-1β处理导致ACSCs出现衰老相关表型,包括增殖减慢(P<0.05)、SA-β-gal染色阳性细胞增加(P<0.05)、p53和p21蛋白水平升高(P<0.05)、SASP因子il-6、Mmp-13和Mmp-3 m RNA水平升高(P<0.05)。进一步研究发现,IL-1β可以导致ACSCs中线粒体膜电位降低(P<0.05),ROS增加(P<0.05),而采用抗氧化剂NAC处理可以明显缓解IL-1β导致的ACSCs中ROS增加和ACSCs衰老相关表型(P<0.05)。结论IL-1β通过诱导氧化应激促进ACSCs衰老,这为从抑制ACSCs衰老和拮抗ACSCs氧化应激损伤角度治疗骨关节炎提供了实验依据。展开更多
文摘The uterus in early pregnancy is a non-lymphoid organ that is enriched in natural killer （NK） cells. Studies to address the role of these abundant human NK cells at the maternal/fetal interface have focused on their response to the major histocompatibility complex （MHC） molecules on fetal trophoblast cells that they contact. The interaction of maternal NK cell receptors belonging to the killer cell immunoglobulin-like receptor （KIR） family with trophoblast MHC class I molecules in pregnancy can regulate NK cell activation for secretion of pro-angiogenic factors that promote placental development. This review will cover the role of KIR at the maternal/fetal interface and focus on KIR2DL4, a KIR family member that is uniquely poised to play a role in pregnancy due to the restricted expression of its ligand, human leukocyte antigen （HLA）-G, by fetal trophoblast cells early in pregnancy. The pathways by which KIR2DL4-HLA-G interactions induce the cellular senescence of NK cells and the role of the resulting senescence-associated secretory phenotype （SASP） in vascular remodeling will be discussed in the context of reproduction.
文摘目的探讨炎症因子白介素-1β(interleukin-1β,IL-1β)对软骨表层细胞(articular cartilage superficial zone cells,ACSCs)衰老的调控作用和相关机制。方法用纤连蛋白黏附法分离培养ACSCs,根据实验分为对照组和IL-1β处理组,采用MTT检测细胞增殖情况,衰老相关-β-半乳糖苷酶(SA-β-gal)染色检测SA-β-gal阳性细胞数,Western blot检测p21和p53蛋白水平,实时荧光定量PCR(RT-qPCR)检测衰老相关分泌表型(senescence-associated secretory phenotype,SASP)因子il-6、Mmp-3和Mmp-13 m RNA水平,CellROX试剂检测活性氧(reactive oxygen species,ROS)水平,JC-1试剂检测线粒体膜电位。最后,取ACSCs设IL-1β处理组和IL-1β+N-乙酰半胱氨酸(N-acetylcysteine,NAC)处理组,检测NAC处理后对IL-1β引起的细胞ROS水平、细胞增殖、SA-β-gal阳性细胞数、p21和p53蛋白水平和SASP分泌因子水平的影响。结果IL-1β处理导致ACSCs出现衰老相关表型,包括增殖减慢(P<0.05)、SA-β-gal染色阳性细胞增加(P<0.05)、p53和p21蛋白水平升高(P<0.05)、SASP因子il-6、Mmp-13和Mmp-3 m RNA水平升高(P<0.05)。进一步研究发现,IL-1β可以导致ACSCs中线粒体膜电位降低(P<0.05),ROS增加(P<0.05),而采用抗氧化剂NAC处理可以明显缓解IL-1β导致的ACSCs中ROS增加和ACSCs衰老相关表型(P<0.05)。结论IL-1β通过诱导氧化应激促进ACSCs衰老,这为从抑制ACSCs衰老和拮抗ACSCs氧化应激损伤角度治疗骨关节炎提供了实验依据。
