基质细胞衍生因子1α—CXCR4趋化THP-1细胞迁移及氧化型低密度脂蛋白的影响
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第38批中国博士后基金(2005038472);;教育部重点科技基金(104158);;湖南省自然科学基金(06jj5051)


The Chemotactic Activity of Stromal Cell Derived Factor 1α—CXCR4 to the Migration of THP-1 Cell and Enhanced Effect of Oxidized Low Density Lipoprotein
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    摘要:

    目的探讨基质细胞衍生因子1α对单核细胞趋化作用、氧化型低密度脂蛋白对基质细胞衍生因子1α趋化单核细胞的影响及其对THP-1细胞表达CXCR4的影响。方法用Transwell迁移实验检测基质细胞衍生因子1α对单核细胞的趋化作用,逆转录聚合酶链反应检测CXCR4mRNA的表达,Western blot检测CXCR4蛋白的表达,并观察氧化型低密度脂蛋白对THP-1细胞CXCR4表达的剂量和时间效应。结果基质细胞衍生因子1α呈浓度依赖性诱导单核细胞迁移,加入CXCR4抗体可明显抑制这种作用。经不同浓度氧化型低密度脂蛋白处理48h后的THP-1细胞再用10μg/L基质细胞衍生因子1α进行趋化时,氧化型低密度脂蛋白呈浓度依赖性地增加单核细胞的迁移,50mg/L氧化型低密度脂蛋白组迁移的细胞数是对照组的11倍。THP-1细胞有基础水平的CXCR4表达,50mg/L氧化型低密度脂蛋白可使CXCR4的表达上调4~5倍。CXCR4上调最早在6h内发生,12h达峰值。结论基质细胞衍生因子1α-CXCR4参与趋化单核细胞迁移,其作用被氧化型低密度脂蛋白加强;氧化型低密度脂蛋白上调CXCR4表达。

    Abstract:

    Aim To explore the effect of stromal cell derived factor 1α—CXCR4(SDF-1α—CXCR4)on THP-1 cells chemotaxis,the influence of oxidized low density lipoprotein(ox-LDL)on THP-1 cells migration exposed to SDF-1α,and the effect of ox-LDL on the expression of CXCR4 in THP-1 cell.Methods THP-1 cells chemotaxis was examined with transwell permeable supports.CXCR4 mRNA and protein was revealed by RT-PCR and Western blot respectively in THP-1 cells incubated with different concentrations/time of ox-LDL.Results SDF-1α induced a pronounced migration of input cells in a concentration-related manner,but this effect was obviously inhibited by the antibody to CXCR4.After pretreated with different concentration of ox-LDL for 48 h,THP-1 cells were exposed to 10 μg/L SDF-1α,ox-LDL enhanced THP-1 cells migration in a concentration-dependent manner and 50 mg/L ox-LDL support 11 fold higher of cells migration.CXCR4 was constitutionally expressed in THP-1 cells.Compared with the control group,a four-to-five fold induction of CXCR4 occurred in THP-1 treated with 50 mg/L ox-LDL.The up-regulation effect was monitored within 6 h,it was peaked at 12 h,then followed with a decline,which mirrored the expression pattern of CXCR4 in monocyte.Conclusions SDF-1α/CXCR4 is implicated in chemotaxis of THP-1 cell and chemotactic response of monocyte to SDF-1α is enhanced by ox-LDL;ox-LDL up-regulates CXCR4 expression.

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吕运成,王佐,危当恒王佐,姜志胜,万炜,李国华,童中艺,王贵学.基质细胞衍生因子1α—CXCR4趋化THP-1细胞迁移及氧化型低密度脂蛋白的影响[J].中国动脉硬化杂志,2007,15(1):15~18.

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  • 收稿日期:2006-09-08
  • 最后修改日期:2007-01-02
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