9-顺式维甲酸部分抑制脂多糖诱导小鼠巨噬细胞系RAW264.7向树突样细胞分化
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国家自然科学基金(30670880,30600242);;上海市科委基础研究重点项目(05JC14037)


9-cis Retinoid Acid Partly Prevents Lipopolysaccharide Induced Cell Differentiation of RAW264.7 Murine Macrophage Cell Line into Dendritic Like Cells
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    摘要:

    目的探讨激活视黄醇类X受体对脂多糖诱导巨噬细胞向树突状细胞分化的影响及其机制。方法小鼠巨噬细胞系RAW264.7经脂多糖诱导48h后分化为树突样细胞,观察同时给予视黄醇类X受体激动剂9-顺式维甲酸对脂多糖诱导分化的干预作用并检测细胞内活性氧的生成,相差显微镜观察细胞形态,流式细胞仪检测与树突状细胞免疫成熟和激活有关的细胞表面标志物(CD40、CD86和CD83),CM-H2DCFDA荧光探针测定细胞内活性氧浓度。结果9-顺式维甲酸部分抑制脂多糖诱导出现的树突样细胞形态改变,使被脂多糖诱导上调的细胞表面标志物CD40、CD86和CD83分别下降约50%、40%和38%,作用表现剂量依赖性;脂多糖引起细胞内活性氧浓度显著升高(平均荧光强度98.9±9.6比12.3±1.8,p<0.05),9-顺式维甲酸在10-8mol/L和10-7mol/L剂量水平分别降低平均荧光强度到69.4±5.8和37.0±4.2,较脂多糖单独处理组差异有显著性(p<0.05)。结论激活视黄醇类X受体能够部分抑制脂多糖诱导巨噬细胞向树突状细胞分化,其机制可能与减轻细胞氧化应激损伤有关。

    Abstract:

    Aim To investigate the effect and mechanism of retinoid X receptor agonist 9-cis retinoid acid on the differentiation of macrophage into dendritic cell induced by LPS. Methods LPS-treated RAW264.7 murine macrophage cell line differentiated into dendritic like cells after 48h. The effect of 9-cisRA on the differentiation induced by LPS was studied. Cell morphology was observed by phase contrast microscope and cell surface markers involved in dendritic cell immune maturation and activation (CD40, CD86, CD83) was analyzed by FACS. Cellular reactive oxygen species production was detected by CM-H2DCFDA fluorescent probe. Results 9-cisRA partly prevented dendritic like morphology induced by LPS. Upregulated cell surface markers CD40、CD86 and CD83 by LPS were decreased about 50%、40% and 38% respectively by 9-cisRA. And the effect of 9-cisRA was dose dependent. LPS-treated RAW264.7 acquired significantly increasing cellular reactive oxygen species (MFI 98.9±9.6 vs 12.3±1.8,p<0.05), which was significantly reduced by 9-cisRA at 10-8M and 10-7M to 69.4±5.8 and 37.0±4.2 respectively. Conclusion RXR agonist 9-cisRA partly inhibits the differentiation of macrophage into dendritic cell induced by LPS, which may be related to reducing oxidative stress injury.

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沈玲红,王彬尧,何奔,曾锦章,周磊,胡刘华,王力,卜军.9-顺式维甲酸部分抑制脂多糖诱导小鼠巨噬细胞系RAW264.7向树突样细胞分化[J].中国动脉硬化杂志,2007,15(5):329~332.

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  • 收稿日期:2006-12-26
  • 最后修改日期:2007-03-10
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