雌二醇调控新西兰黑鼠×白鼠子一代雌鼠的骨髓树突状细胞作用研究  

17β-estradiol modulates bone-marrow derived dendritic cells in （NZBxNZW） F1 female mice

作　　者：姜波[1] 孙凌云[1] 王红[1] 

机构地区：[1]南京大学医学院附属鼓楼医院风湿免疫科,210008

出　　处：《中华风湿病学杂志》2008年第4期234-237,共4页Chinese Journal of Rheumatology

基　　金：江苏省自然科学基金资助项目（BK2006007）;江苏省135医学重点人才基金资助项目

摘　　要：目的通过比较雌二醇（E2）对发病前后系统性红斑狼疮（SLE）模型鼠——新西兰黑鼠×新西兰白鼠子一代（NZB／wF1）雌鼠骨髓来源树突状细胞（BMDC）的作用，探索雌激素参与SLE的作用机制。方法骨髓单个核细胞在重组小鼠粒细胞-巨核细胞集落刺激因子（rmGM-CSF）、重组白细胞介素-4（rmlL-4）、E2和雌激素受体（ER）调节剂——他莫昔芬（TAM）的作用下培养7d诱导分化为未成熟DC，脂多糖（LPS）刺激24h诱导为成熟DC，流式细胞仪检测BMDC表面共刺激分子CD40及胞内IL-6、IL-10、IL-12和肿瘤坏死因子（TNF）-α的产生，混合淋巴细胞反应检测BMDC对脾脏T淋巴细胞的刺激功能。结果E2升高未成熟DC，但降低成熟DCCD40的表达；E2增强未成熟DC，但降低成熟DC的淋巴细胞刺激功能；E2降低幼龄鼠，但升高高龄鼠BMDC细胞因子的产生。TAM拮抗E2的作用。结论E2通过ER调控狼疮鼠的BMDC，此调控作用随狼疮的进展及细胞的成熟阶段不同而有所不同。Objective To investigate the mechanisms of estrogen in the pathogenesis of systemic lupus erythematosus （SLE）, we compared the effects of 17β-estradiol （E2） on bone marrow （BM）-derived dendritic cells （BMDCs） in （NZB×NZW） F1 （NZB/w F1 ） female mice before and after the disease onset. Methods Immature BMDCs were differentiated from BM monocytes cultured with rmGM-CSF, traiL-4, E2 and estrogen receptor （ER） modulator-tamoxifen （TAM） for 7 days. Then immature DCs were stimulated by LPS for 24h to get mature BMDCs. Flow cytometry was utilized to detect the production of costimulatory molecule CD40 and intracellular IL-6, IL-10, IL-12 and TNFct of DCs. Mixed lymphocytes reaction was used to measure the stlm- ulatory activity of DCs on spleen T lymphocytes. Results E2 mainly increased the expression of CD40 on immature BMDCs but reduced its expression on mature BMDCs. E2 enhanced the stimulatory activity of immature BMDCs, but weakened the activity of mature BMDCs. E2 decreased the production of cytokines of BMDCs in young mice, but increased them in old mice. Conclusion E2 modulates the functions of BMDCs of lupus model mice by binding with ER. The modulation varies depending on disease progression and cell maturation status.

关 键 词：雌二醇 树突细胞 骨髓 (NZBxNZW)F1鼠 

分 类 号：R686[医药卫生—骨科学]