摘要
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。
Abstract
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 cells stimulatory proliferation capacity， and IL-10， IL-12 and INF-γ production. 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-1 could 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 1.0 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 cells.
关键词
树突状细胞 /
丁酸钠 /
免疫耐受
{{custom_keyword}} /
Key words
dendritic cell /
sodium butyrate /
immunotolerance
{{custom_keyword}} /
刘璐 李琳c 闵军 王捷 曾育杰 伍衡 陈双 褚忠华.
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[J]. 中国药学杂志, 2011, 46(24): 1874-1878
LIU Lu;LI Linc;MIN Jun;WNG Jie;ZENG Yu-jie;WU Heng;CHEN Shung;CHU Zhong-hu.
Comparison of the Immunological Effect of Sodium Butyrate of Different Concentrations on the Differentiation of Dendritic Cells[J]. Chinese Pharmaceutical Journal, 2011, 46(24): 1874-1878
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] ONAI N， MANZ M G. The STATs on dendritic cell development[J]. Immunity， 2008， 28(4)： 490-492.
[2] BARRATT-BOYES S M， THOMSON A W. Dendritic cells： tools and targets for transplant tolerance[J]. Am J Transplant， 2005， 5(12)： 2807-2813.
[3] NOURI-SHIRZAI M， THOMSON A W. Dendritic cells as promoters of transplant tolerance[J]. Expert Opin Biol Ther， 2006， 6(4)： 325-339.
[4] HIKAWA H， LOTZE M T， ROSENBLUM W D. Induction of peripheral tolerance by local delivery of dendritic cell progenitors to cardiac allografts in a murine heterotopic heart transplantation model[J]. Gen Thorac Cardiovasc Surg， 2007， 55(8)：307-314.
[5] FANG Y， GENG L， DONG S， et al. Effects of cyclosporine A on murine bone marrow-derived dendritic cells[J].Chin Pham J(中国药学杂志)， 2006， 41(13)：983-986.
[6] CAYO M A， CAYO A K， JARJOUR S M， et al. Sodium butyrate activates Notch1 signaling， reduces tumor markers， and induces cell cycle arrest and apoptosis in pheochromocytoma[J]. Am J Transl Res， 2009， 1(2)：178-183.
[7] LIU L， MIN J， WANG J， et al. Study on the immunological function of sodium butyrate-induced immature human monocyte-derived dendritic cells[J]. Chin J Patho-Physiol (中国病理生理杂志)， 2007， 23(6)：1199-1203.
[8] GAGLIARDI M C， TELONI R， GIANNONI F， et al. Mycobacterium bovis Bacillus Calmette-Guerin infects DC-SIGN- dendritic cell and causes the inhibition of IL-12 and the enhancement of IL-10 production[J]. J Leukoc Biol， 2005， 78(1)： 106-113.
[9] FU F， LI Y， QIAN S， et al. Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+， CD80dim， CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients[J]. Transplantation， 1996， 62 (5)：659-665.
[10] KHAN T A， PEH K K. A preliminary investigation of chitosan film as dressing for punch biopsy wounds in rats[J]. J Pharm Sci， 2003， 6(1)： 20-26.
[11] DELEMARRE F G， HOOGEVEEN P G， DE HAAN-MEULMAN M， et al. Homotypic cluster formation of dendritic cells， a close correlate of their stage of maturation[J]. J Leukoc Biol， 2001， 69 (3)： 373-380.
[12] SAEMANN M D， PAROLINI O， BOHMIG G A， et al. Bacterial metabolite interference with maturation of human monocyte-derived dendritic cells[J]. J Leukoc Biol， 2002， 71(2)： 238 -246.
[13] NENCIONI A， BECK J， WERTH D， et al. Histone deacetylase inhibitors affect dendritic cell differentiation and immunogenicity[J]. Clin Cancer Res， 2007， 13(13)： 3933-3941.
[14] MILLARD A L， MERTES P M， ITTELET D， et al. Butyrate affects differentiation， maturation and function of human monocyte-derived dendritic cells and macrophages[J]. Clin Exp Immunol， 2002， 130(2)： 245-255.
[15] DIAKOS C， PRIESCHL E E， SAEMANN M， et al. Novel mode of interference with nuclear factor of activated T-cells regulation in T-cells by the bacterial metabolite n-butyrate[J]. J Biol Chem， 2002， 277(27)： 24243-24251.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(756 KB)
