雷帕霉素对大鼠髓源性树突状细胞表型和功能的影响

目的 观察雷帕霉素(RAPA)对树突状细胞(DC)表型和功能的影响.方法 诱导分化Lewis大鼠骨髓源性DC,第6天同时加入脂多糖(LPS)和10μg／L或100 μg/L RAPA,48 h后检测共刺激分子、细胞凋亡、上清液白细胞介素(IL) -10和IL-12水平；混合淋巴细胞培养观察DC刺激Brown Norway大鼠T淋巴细胞增殖能力.结果 RAPA能抑制DC成熟,共刺激分子的上调显著受抑,细胞凋亡增加,100 μg/L RAPA组DC凋亡率达53％.DC在脂多糖作用下分泌IL-10、IL-12上升至( 1533±117)、(2575 ±58) ng/L,但同时加入100μg/L RAPA后,两者下降至(330±159)、( 245±63) ng/L.RAPA处理的DC对T淋巴细胞增殖有抑制作用.结论 雷帕霉素能抑制DC成熟并诱导其凋亡,RAPA处理的DC分泌细胞因子降低,且抑制T淋巴细胞增殖.

Influences of rapamycin on phenotype and function of rat bone marrow-derived dendritic cells in

Objective To observe the effect of rapamycin (RAPA) on the phenotype and functional activities of dendritic cells (DC) in vitro.Methods Bone marrow mononuclear cells of Lewis rats were induced and differentiated in vitro.On the day 6,lipopolysaccharide (LPS) and 10 μg/L or 100 μg/L RAPA were added to the culture concomitantly.Fourty-eight h later,co-stimulatory molecule expression,apoptosis,intedeukin (IL) -12 and IL-10 levels in the supematant were detected.Mixed lymphocyte reaction (MLR) was performed.Brown Norway rat splenocytes were used as responders.Results RAPA significantly inhibited the up-regulated expression of co-stimulatory molecules.RAPA induced DC apoptosis.The increased production of IL-10 and IL-12 by DC in response to LPS was decreased in the presence of PAPA [from (1533 ±117) ng/L and (2575 ±58) ng/L to (330 ±159) ng/L and (245 ±63) ng/L in the presence of 100 μg/L RAPA,respectively].Moreover,DC treated with PAPA had an inhibitory effect on T cell proliferation in MLR.Conclusion PAPA impacts the phenotypic maturation,induces apoptosis,inhibits cytokine production,and inhibits the allostimulatory activity of DC.