不同浓度丁酸钠诱导未成熟树突状细胞分化的免疫学功能比较

Comparison of the Immunological Effect of Sodium Butyrate of Different Concentrations on the Differentiation of Dendritic Cells

目的探讨不同浓度丁酸钠诱导对于体外培养的树突状细胞(dendritic cells,DC)免疫刺激活性的影响。方法通过重组人粒细胞-巨噬细胞集落刺激因子(GM-CSF)和人重组白细胞介素4(IL-4)体外诱导的人单个核细胞来源的DC,按照0.5、0.75、1、1.25、1.5 mmol.L-15种浓度丁酸钠体外诱导分化,并分别以流式细胞仪,FITC-dxtran内吞检测、MLR、ELISA法检测DC的凋亡率、表面标志、内吞能力、刺激淋巴细胞增殖能力和IL-10、IL-12、INF-γ分泌的变化。结果 1.25、1.5 mmol.L-1丁酸钠有较高的细胞毒性。0.5、0.75、1 mmol.L-1丁酸钠均可抑制DC表面成熟表型的表达。其中以1.0 mmol.L-1丁酸钠诱导下DC不成熟表型表达效果最稳定。虽然不同浓度丁酸钠诱导下的DC内吞能力无显著差异(P>0.05),但1.0 mmol.L-1丁酸钠与0.5、0.75 mmol.L-1丁酸钠相比较其IL-10分泌量(3.29±0.21)最大,抑制淋巴细胞增殖能力(1.53±1.04)最强(P<0.05)。结论 1.0 mmol.L-1丁酸钠是诱导DC稳定不成熟状态的最佳浓度。

OBJECTIVE To investigate the immunological effects of different concentrations of sodium butyrate on dendritic cells （DC） differentiation in vitro. METHODS Human monocyte-derived DC were induced in the presence of cytokine recombined human granulocyte macrophage colony-stimulating factor （GM-CSF） and interleukin （IL） -4. The effects of different concentrations of sodium butyrate on DC were detected by FCM, endocytic activity, T ceils stimulatory proliferation capacity, and IL-10, IL-12 and INF-γ pro-duction. RESULTS Sodium butyrate of 1.25 and 1.5 mmol . L-1 had much higher toxicity on DC compared with sodium butyrate below 1 mmol . L-1. All three concentrations of sodium butyrate below 1 mmol .L- -1could down-regulate the major histocompatibility complex （MHC） class II and costimulatory molecules of DC. Sodium butyrate of 1 mmol . L- 1. had better suppression effects on mature markers of DC than other groups （0. 5 and 0. 75 mmol . L-1 ）, although the endocytic activity of DC had no significant differences among the three groups （P 〉 0. 05 ）. Sodium butyrate of I. 0 mmol . L- 1 had the strongest capacity to induce a stage of T-cell anergy （ 1.53± 1.04） and promote IL-10 production （3.29 ±0. 21 ） compared with those of 0. 5 and 0. 75 mmol .L-1 sodium butyrate. CONCLUSION 1.0 mmol . L- 1 is the most effective concentration of sodium butyrate for inducing immaturation state of dendritic ceils.