摘要
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,100μg/L)和重组人白细胞介素4(IL-4,20μg/L)的RPMI1640培养5天,使其分化为未成熟DC。先经罗格列酮(50μmol/L)干预24h后,加入糖基化-人血清白蛋白(AGE-HSA,200μg/ml)再干预48h,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。
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.
出处
《南京医科大学学报（自然科学版）》
CAS
CSCD
北大核心
2008年第6期767-770,共4页
Journal of Nanjing Medical University(Natural Sciences)
基金
江苏省医学领军人才基金资助
