罗格列酮抑制糖基化-人白蛋白诱导的人单核细胞源树突状细胞的免疫成熟
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江苏省医学领军人才基金资助


Rosiglitazone inhibits advanced glycosylation end-human serum albumin induced immune maturation of dendritic cells
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    目的:研究过氧化物酶体增殖物激活受体-γ(PPAR-γ)激动剂罗格列酮(rosiglitazone)对糖基化终产物(AGEs)诱导的人单核细胞源树突状细胞(DC)的免疫成熟的影响-方法:采用免疫磁珠法分离人外周血CD14+单核细胞,经含重组人粒细胞—巨噬细胞集落刺激因子(GM-CSF,100 μg/L)和重组人白细胞介素4(IL-4,20 μg/L)的RPMI1640 培养5 天,使其分化为未成熟DC-先经罗格列酮(50 μmol/L)干预24 h后,加入糖基化-人血清白蛋白(AGE-HSA,200 μg/ml)再干预48 h,采用流式细胞术检测树突状细胞表型(CD1a-CD80-CD86 和HLA-DR),混合T 淋巴细胞反应检测DC对淋巴细胞增殖的影响,酶联免疫吸附法检测细胞培养上清白细胞介素10(IL-10)-白细胞介素12(IL-12)-肿瘤坏死因子α(TNF-α)和γ干扰素(INF-γ)的浓度-结果:与对照组相比,经罗格列酮处理的DC可明显下调由AGE-HSA促进的CD80-CD86-HLA-DR 和CD1a的表达,使AGE-HSA促进的对T 淋巴细胞的增殖作用明显减弱,明显抑制DC细胞因子IL-10-IL-12-TNF-α和IFN-γ的分泌(P < 0. 05)-结论:过氧化物酶体增殖物激活型受体γ激动剂罗格列酮可以抑制糖基化-人血清白蛋白诱导的树突状细胞的免疫成熟及其免疫功能,这可能是它抗炎的重要机制之一-

    Abstract:

    Objective:To investigate the effect of peroxisome proliferator activated receptors-γ(PPAR-γ) agonist Rosiglitazone on the immune maturation of monocyte-derived dendritic cell(DC) induced by advanced glycosylation end products(AGEs). Methods:Monocytes were purified(over 98%) using Anti-CD14 microbeads. After cultured with DC Cellgro medium containing recombinated human granulocyte-macrophage colony stimulating factor(rhGM-CSF)(100 μg/L) and recombinated human interleukin-4(rhIL-4)(20 μg/L) for 5 days,monocytes were derived into immature DC. Rosiglitazone(50 μmol/L) was added to the medium for 24 hours. The advanced glycosylation end-human serum albumin(AGE-HSA)(200 μg/ml) was then added to the medium for another 48 hours. The expressions of(CD1a,CD80,CD86 and HLA-DR) were analyzed by FACS,and the cytokines secretions of culture supernatants(IL-10,IL-12,TNF-α and INF-γ) were measured by ELISA. Results:Rosiglitazone reduced AGE-HSA inducing expressions of CD1a,CD80,CD86 and HLA-DR,and also inhibited AGE-HSA inducing T-cell stimulatory activity. The cytokines secretions of DCs induced by AGE-HSA were significantly attenuated by Rosiglitazone. Conclusion:The study suggested that one of the anti-inflammatory mechanisms of PPAR-γ agonist Rosiglitazone should be mediated by inhibiting the AGEs induced maturation and immune function of DCs.

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贾庆哲,杨志健,朱铁兵,王连生,李春坚,王 晖,陈 波,马文珠,曹克将.罗格列酮抑制糖基化-人白蛋白诱导的人单核细胞源树突状细胞的免疫成熟[J].南京医科大学学报(自然科学版),2008,28(6):767-770

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  • 收稿日期:2008-02-14
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