基础医学与临床 ›› 2015, Vol. 35 ›› Issue (6): 786-791.

• 研究论文 • 上一篇    下一篇

来那度胺可抑制单核细胞向M2型巨噬细胞分化及相关细胞因子的分泌

魏冲1,姜志超2,王昊天2,张薇3,李天骄2,汪玄4,周道斌3   

  1. 1. 北京协和医院
    2. 北京协和医院 血液内科
    3. 中国医学科学院 北京协和医学院 北京协和医院
    4. 北京协和医院血液科
  • 收稿日期:2014-05-12 修回日期:2014-12-29 出版日期:2015-06-05 发布日期:2015-05-27
  • 通讯作者: 周道斌 E-mail:daobinzhou@yahoo.com
  • 基金资助:
    北京自然基金

Lenalidomide significantly inhibit the differentiation of monocytes to M2 polarized macrophages and down-regulate secretion of associated cytokines

  • Received:2014-05-12 Revised:2014-12-29 Online:2015-06-05 Published:2015-05-27
  • Contact: Dao-bin ZHOU E-mail:daobinzhou@yahoo.com

摘要: 目的 探索来那度胺在肿瘤微环境中对于单核细胞向M2型巨噬细胞分化及IL-10、VEGF和TGF-β1水平的影响。方法 密度梯度离心法分离初治淋巴瘤患者及健康志愿者外周血单个核细胞(PBMC)。用Transwell24孔板共培养PBMC与淋巴瘤细胞株HUT-78,并于共培养体系中加入来那度胺。流式细胞术分析肿瘤相关巨噬细胞(TAM)特征性表型CD68和CD163的表达,ELISA法检测共培养体系细胞因子IL-10、VEGF和TGF-β1的含量。结果 在PBMC与HUT-78构成的体外共培养体系中加入来那度胺后,CD68+、CD163+、CD68+CD163+细胞及CD68+CD163+在CD68+细胞中所占比例均有显著的下降(P<0.05)。加入来那度胺后患者组CD68+CD163+/ CD68+比例下降程度明显高于健康志愿者(P<0.05)。加入来那度胺的患者共培养组相对于未加来那度胺的共培养组IL-10和VEGF水平均有显著下降(P<0.01,P<0.05)。结论 来那度胺在PBMC与淋巴瘤细胞构建的体外共培养体系中能够有效抑制单核细胞向M2型TAM的分化,且能够抑制患者组共培养体系中IL-10、VEGF分泌。

关键词: 关键词 来那度胺, 淋巴瘤, 肿瘤相关巨噬细胞

Abstract: Objective To explore the impact of anti-cancer drug Lenalidomide on the differentiation of monocytes to M2 polarized macrophages and the secretion of IL-10、VEGF and TGF-β1. Methods The peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density gradient centrifugation from peripheral blood of both lymphoma patients and healthy controls. Then PBMCs were co-cultured with HUT-78 lymphoma cells in Transwell 24-well plates. Anti-cancer drug Lenalidomide was added to the co-culture system. Expressions of the markers of TAMs (CD68 and CD163) were tested by flow cytometry. IL-10, VEGF and TGF-β1 level in the co-culture system were detected by ELISA. Results Treatment with Lenalidomide significantly decreased the proportion of CD68+, CD163+,CD68+CD163+ cells and the proportion of CD68+CD163+ / CD68+cells(P<0.05). The degree of decline of CD68+CD163+ / CD68+cells was more significant in patients than that in healthy controls(P<0.05). For patients, treatment with Lenalidomide significantly decreased the IL-10 and VEGF level in the co-culture system(P<0.01,P<0.05). Conclusion Lenalidomide significantly inhibits the differentiation of monocytes to M2 polarized macrophages and down-regulate the secretion of IL-10 and VEGF in the co-culture system in patients group.

Key words: Key words Lenalidomide, Lymphoma, Tumor-associated macrophage

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