Extracellular branched-chain amino acids, especially valine, regulate maturation and function of monocyte-derived dendritic cells
Extracellular branched-chain amino acids, especially valine, regulate maturation and function of monocyte-derived dendritic cells
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DOI：
10.4049/jimmunol.179.10.7137
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Shimosegawa, Tooru
中科院分区：
文献类型：
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作者：
Kakazu, Eiji;Kanno, Noriatsu;Shimosegawa, Tooru
肝硬变患者树突状细胞(DC)功能受损。众所周知，肝硬变患者血浆支链氨基酸(BCAA)水平降低。虽然氨基酸在许多器官中与维持细胞结构和功能有关，但关于氨基酸(包括支链氨基酸)在免疫系统中的作用的数据有限。本研究旨在探讨支链氨基酸在人单核细胞来源的树突状细胞(MoDC)功能中的作用。从健康志愿者和丙型肝炎患者外周血中分离出CD14阳性单核细胞(CD14(+))。在不含支链氨基酸或缬氨酸的培养液中，单核细胞可以分化为未成熟的DC，但不能分化为成熟的DC，CD83的表达较弱。剥夺亮氨酸或异亮氨酸不影响这一过程。去掉支链氨基酸或缬氨酸的培养液中，MoDC的同种异体刺激能力显著降低(P=0.017，P=0.012，Bonferroni‘s分析)。Annexin V-FITC/碘化丙啶染色显示，在任何条件下DC产量和存活率均无显著差异。免疫印迹结果显示，缺乏Valine或Leucine会降低磷酸化S6蛋白的表达。Valine可剂量依赖性地增加健康志愿者和丙型肝炎肝硬变患者MoDC的同种异体刺激能力和IL-12的产生。升高胞外Valine浓度可改善肝硬变患者的DC功能。这些数据为可能有益于肝硬变患者的营养治疗提供了理论依据。
The functions of dendritic cells (DCs) are impaired in patients with liver cirrhosis. It is well-known that cirrhotic patients show decreased levels of plasma branched-chain amino acids (BCAA). Although amino acids are associated with maintaining the cell structure and function in many organs, limited data are available regarding the role of amino acids including BCAA in the immune system. We aimed to investigate the roles of BCAA in the function of human monocyte-derived DCs (MoDC). CD14-positive monocytes (CD14(+)) were isolated from PBMC from healthy volunteers and hepatitis C virus (HCV) cirrhotic patients. In medium deprived of BCAA or valine, monocytes were able to differentiate into immature, but not into mature, DCs and showed weak expression of CD83. The deprivation of leucine or isoleucine did not affect this process. The MoDC allostimulatory capacity was significantly decreased in medium deprived of BCAA or valine (p = 0.017, p = 0.012, Bonferroni's analysis, respectively). Annexin V-FITC/Propidium iodide staining showed that the DC yield and viability were not significantly different under any medium. Immunoblotting demonstrated that depletion of valine or leucine decreased phospho-S6 kinase expression. Valine increased dose-dependently the allostimulatory capacity and IL-12 production of MoDC from both healthy volunteers and HCV cirrhotic patients. An elevated extracellular concentration of valine could improve the DC function in cirrhotic patients. These data provide a rationale for nutrition therapy that could be beneficial to patients with cirrhosis.