普伐他汀对人单核细胞源树突状细胞免疫功能的影响  

Pravastatin inhibits immunological function of human monocyte-derived dendritic cells: a new immunomodulatory property of statins

作　　者：梁春[1] 贾庆哲[2] 罗育坤[2] 黄东[2] 许从峰[2] 王克强[2] 吴宗贵[1] 葛均波[2] 

机构地区：[1]第二军医大学附属长征医院心内科,上海200003 [2]复旦大学附属中山医院上海市心血管病研究所

出　　处：《上海医学》2005年第4期274-277,共4页Shanghai Medical Journal

基　　金：国家重点基础研究发展规划(G2000056903);上海市科委(02JC14026)资助项目

摘　　要：目的探讨普伐他汀对在免疫调控中起重要作用的人单核细胞源树突状细胞(DC)免疫功能的影响.方法采用免疫磁珠法分离人外周血CD14+单核细胞,经含重组粒细胞-巨噬细胞刺激因子(100 ng/ml)和重组白介素(rhIL)-4(20 ng/ml)的Cellgro培养,使其分化为DC.DC与50～100 μmol/L普伐他汀孵育72 h后,采用流式细胞术检测DC表型(CD1a、CD40、CD86、HLA-DR),混合T淋巴细胞反应检测DC对淋巴细胞增殖的影响,采用酶联免疫吸附试验法检测细胞培养上清液中Th1/Th2 [白介素(IL)-12、干扰素(IFN)-γ/ IL-2、IL-10]细胞因子的浓度.结果与对照组相比,经普伐他汀处理的DC可下调CD80、CD86、 HLA-DR和CD1a的表达,对T淋巴细胞增殖作用明显减弱,明显抑制DC Th1细胞因子IL-12和IFN-γ的分泌(P<0.05),但对Th2细胞因子IL-2 和IL-10水平无明显影响.100 μmol/L甲羟戊酸可逆转普伐他汀的作用.结论普伐他汀可明显抑制DC的成熟和免疫活性,此作用与甲羟戊酸途径有关.这可能是他汀类药物免疫调节的新机制.Objective To appraise the effects of pravastatin on immunological function of human monocyte-derived dendritic cells (DC).Methods Human monocytes were purified using Anti-CD14 microbeads after 5 days culture with DC Cellgro medium containing 100 ng/ml rhGM-CSF and 40 ng/ml rhIL-4, immature DC was then obtained. Drug as 50-100 μmol/L pravastatin, 100 μmol/L mevolonate and 100 μmol/L pravastatin+ mevolonate were added to the medium for 72 hours. FACS was used to investigate the immunophenotypic expression (CD1a, CD40, CD86 and HLA-DR), The Th1/Th2 (IL-12、IFN-γ/IL-2、IL-10 )cytokines concertrations of cultured supernatants were measured with ELISA.Results Pravastatin reduced LPS-induced immunophenotypic expressions of DC (CD40, CD1a, CD86 and HLA-DR), and also inhibited its T-cell stimulatory activity. The Th1 (IL-12、IFN-γ) cytokine secretion of DC was significantly attenuated by pravastatin, but the Th2 (IL-2、IL-10) cytokine secretion was not affected. Mevalonate added in vitro could reverse the effects of pravastatin.Conclusions Our study suggests that pravastation can significantly inhibit maturation and immunoactivity of DC which may be related to the mevalonate pathway showing a new immunomodulating mechanism on statins series.

关 键 词：普伐他汀 细胞免疫功能 细胞源 CD14^+单核细胞 干扰素(IFN)-Γ 酶联免疫吸附试验法 巨噬细胞刺激因子 流式细胞术检测 T淋巴细胞反应 细胞培养上清液 Thl细胞因子 Th2细胞因子 mol/L 淋巴细胞增殖 HLA-DR 细胞增殖作用 

分 类 号：R96[医药卫生—药理学]