丹皮酚对FSL-1与IL-4共刺激诱导树突状细胞成熟及细胞因子表达的影响

doi:10.12092/j.issn.1009-2501.2019.01.003

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (1): 14-19.doi: 10.12092/j.issn.1009-2501.2019.01.003

丹皮酚对FSL-1与IL-4共刺激诱导树突状细胞成熟及细胞因子表达的影响

胡玉平¹，周海云²，黄巧玲¹，姚轶敏³

¹杭州市第三人民医院药学部，杭州 310009，浙江； ²浙江大学医学院附属第二医院药剂科，杭州 310009，浙江；³浙江中医药大学附属第一医院检验科，杭州 310006，浙江

收稿日期:2018-10-15 修回日期:2018-11-26 出版日期:2019-01-26 发布日期:2019-01-25
通讯作者: 黄巧玲，女，本科，主任药师，研究方向：医院药学。 Tel：0571-87827545 E-mail：HQL6512@163.com
作者简介:胡玉平，女，本科，主管药师，研究方向：医院药学。 Tel：0571-87827545 E-mail：79942109@qq.com
基金资助:
杭州市卫生局资助项目（2016A25）

Effect of paeonol on the expression of cytokines production and maturation of DCs co-stimulated by FSL-1 and IL-4

HU Yuping¹, ZHOU Haiyun², HUANG Qiaoling¹, YAO Yimin³

¹ Pharmaceutical Department, Hangzhou Third People's Hospital, Hangzhou 310009, Zhejiang, China; ²Department of Pharmacy, The Second Affiliated Hospital of Medical College of Zhejiang University, Hangzhou 310009, Zhejiang, China; ³Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou 310006, Zhejiang, China

Received:2018-10-15 Revised:2018-11-26 Online:2019-01-26 Published:2019-01-25

摘要/Abstract

摘要：

目的: 研究牡丹皮提取物丹皮酚对TLR2配体FSL-1刺激诱导慢性前炎因子释放的分子机制，为天然药物治疗慢性皮炎提供新的思路。方法: 将小鼠髓源性树突状细胞（DCs）分成5组，对照组、FSL-1刺激组、丹皮酚低、中、高剂量干预组（25、50、100 μg/mL），所有组均给予10 ng/mL rmIL-4环境培养，ELISA法检测树突状细胞培养上清液中IL-10、IL-12的含量，流式细胞术检测树突状细胞表面MHC-II、CD40和CD86分子表达的水平。结果: 各组树突状细胞表面分子表达水平：刺激组与对照组相比，树突状细胞表面MHC- II、CD40和CD86表达量明显增加（P<0.05）。丹皮酚干预组与刺激组相比，DCs表面MHC- II、CD40和CD86表达量均降低，且高、中剂量组具有统计学差异（P<0.05）。细胞因子分泌水平：刺激组与对照组相比，抗炎性细胞因子IL-10的水平明显降低（P<0.05），而前炎细胞因子IL-12的水平明显升高（P<0.05）；丹皮酚干预组与FSL-1刺激组相比，各个干预组的IL-10的分泌水平显著上升（P<0.05），丹皮酚干预组中IL-12的分泌水平均有下降，但仅高、中剂量组具有统计学差异（P<0.05）。结论: TLR2配体FSL-1可以和IL-4共刺激DCs，促进DCs活化并成熟，促进前炎性因子IL-12释放，抑制IL-10等抗炎细胞因子分泌，诱导CD4+T细胞向Th1分化，导致了Th1极化状态，诱导慢性皮肤炎症；而天然药物丹皮酚可抑制TLR2配体介导TLR2通路活化DCs这一过程，具有抑制皮肤慢性炎症的潜力。

关键词: 丹皮酚, 慢性皮炎, 树突状细胞, 细胞因子, Th1/Th2

Abstract:

AIM: To study the molecular mechanism of natural paeonol induced by TLR2 signal transduction pathway of inflammation of the skin, developing new ideas for prevention and treatment of atopic dermatitis and provide a theoretical basis. METHODS: Bone marrow-derived dendritic cells (BMDCs) were divided into three groups: control group, FSL-1 stimulated group, paeonol treatment group with different concentrations (25, 50, 100 g/mL). The DC surface molecules such as CD40, CD86 and MHC-II were detected by flow cytometry. The cytokine levels of IL-10, IL-12 in culture supernatant were detected by ELISA. RESULTS: The expression of CD40, CD86 and MHC-II on the surface of dendritic cell surface molecules were significantly increased after stimulated with FSL-1 as compared to control group （P<0.05）. After treated with paeonol (50, 100 g/mL), expressions of CD40, CD86 and MHC-II were all decreased, only in the high and middle dose groups, the difference was statistically significant (P<0.05). Compared with the control group, FSL-1 stimulated group significantly enhanced the secretion of pro-inflammatory cytokines IL-12（P<0.05）, while the anti-inflammatory cytokine IL-10 was decreased significantly （P<0.05）. Meanwhile, compared with FSL-1 stimulated group, the levels of IL-12 were found significantly decreased in the middle and high dose of paeonol treatment group（P<0.05）, but the low dose treatment group did not show significant effect（P>0.05）. The above results showed that FSL-1 can change the differentiation of lymphocyte subset through affecting the secretion of DC cytokines, which can promote the pro-inflammatory cytokines such as IL-12 secretion, while the secretion of anti-inflammatory cytokines such as IL-10 were decreased. But paeonol reversed these effects. CONCLUSION: FSL-1, the TLR2 ligands, can promote the development of chronic dermatitis and chronic inflammation of the development through influencing the expression of cytokines production and maturation of DCs. The level of IL-12 is increased while level of IL-10 is decreased by activating the TLR2 signaling pathway. Furthermore, the primitive Th cells are promoted to transform to Th1 thereby resulting in Th1/Th2 polarization. However, paeonol can reverse FSL-1 induced cellular processes, and shows potential in the prevention and treatment of chronic dermatitis.

Key words: paeonol, atopic dermatitis, dendritic cell, cytokine, Th1/Th2

中图分类号:

胡玉平，周海云，黄巧玲，姚轶敏. 丹皮酚对FSL-1与IL-4共刺激诱导树突状细胞成熟及细胞因子表达的影响[J]. 中国临床药理学与治疗学, 2019, 24(1): 14-19.

HU Yuping, ZHOU Haiyun, HUANG Qiaoling, YAO Yimin. Effect of paeonol on the expression of cytokines production and maturation of DCs co-stimulated by FSL-1 and IL-4[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(1): 14-19.

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丹皮酚对FSL-1与IL-4共刺激诱导树突状细胞成熟及细胞因子表达的影响

Effect of paeonol on the expression of cytokines production and maturation of DCs co-stimulated by FSL-1 and IL-4

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