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芍药苷抑制变应原诱导的小鼠树突状细胞的成熟和免疫刺激功能。

Paeoniflorin inhibits the maturation and immunostimulatory function of allergen-induced murine dendritic cells.

机构信息

Department of Dermatology, Jining First People's Hospital, Shandong, PR China; Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu, PR China.

Department of Radiology, Jining First People's Hospital, Shandong, PR China.

出版信息

Int Immunopharmacol. 2014 Apr;19(2):221-32. doi: 10.1016/j.intimp.2014.02.001. Epub 2014 Feb 15.

DOI:10.1016/j.intimp.2014.02.001
PMID:24534772
Abstract

Dendritic cells (DCs) as the front lines of defense play a crucial role in allergic contact dermatitis (ACD). Paeoniflorin (PF) has been clinically proven to be effective in the treatment of inflammatory skin diseases such as ACD. However, the mechanisms underlying the anti-inflammatory effect of PF remain unclear. The aim of this study was to explore the effect of PF on the maturation and immunostimulatory function of DCs in the murine model of ACD in vitro. Murine bone marrow-derived DCs were stimulated with the contact sensitizer 1-chloro-2, 4-dinitrobenze (DNCB) in vitro. Surface antigen expression of DCs (MHC II, CD40, CD80, and CD86), as an indicator of maturation DCs and cytokines (IL-12, IFN-γ, IL-10, and TGF-β) after DNCB stimulation in the absence or presence of PF at different doses, was detected. Then, we detected that PF-treated DCs stimulated T cells in response to DNCB. PF inhibited the up-regulation of MHC II, CD80, CD86, and CD40, decreased IL-12p70 secretion, while increased the production of IL-10 and TGF-β, and had no effect on IFN-γ cytokine production by murine bone marrow-derived DCs in response to DNCB. DCs exposed to PF had diminished capacity to stimulate allogeneic T cell proliferation and to activate IFN-γ-producing CD4⁺ T cells and induced CD4⁺CD25⁺Foxp3⁺ T cells and IL-10-producing T cell expansion from naïve CD4⁺ T cells. These results indicate that PF may be effective in preventing and treating ACD in vitro and other inflammatory responses possibly through inhibiting maturation of DCs and limiting their capacity to stimulate T cell responses.

摘要

树突状细胞 (DCs) 作为第一道防线,在过敏性接触性皮炎 (ACD) 中发挥着关键作用。芍药苷 (PF) 已被临床证明可有效治疗 ACD 等炎症性皮肤病。然而,PF 抗炎作用的机制尚不清楚。本研究旨在探讨 PF 对体外 ACD 小鼠模型中 DC 成熟和免疫刺激功能的影响。体外使用接触致敏剂 1-氯-2,4-二硝基苯 (DNCB) 刺激小鼠骨髓来源的 DC。检测 DC 表面抗原表达 (MHC II、CD40、CD80 和 CD86),作为成熟 DC 的指标,以及在有无不同剂量 PF 存在的情况下,DNCB 刺激后细胞因子 (IL-12、IFN-γ、IL-10 和 TGF-β) 的表达。然后,我们检测到 PF 处理的 DC 可刺激 T 细胞对 DNCB 产生反应。PF 抑制 MHC II、CD80、CD86 和 CD40 的上调,减少 IL-12p70 的分泌,同时增加 IL-10 和 TGF-β 的产生,但对 IFN-γ 细胞因子的产生没有影响由 DNCB 刺激的小鼠骨髓来源的 DC。暴露于 PF 的 DC 刺激同种异体 T 细胞增殖的能力减弱,激活 IFN-γ 产生的 CD4 ⁺ T 细胞的能力减弱,并诱导幼稚 CD4 ⁺ T 细胞中 CD4 ⁺ CD25 ⁺ Foxp3 ⁺ T 细胞和 IL-10 产生 T 细胞的扩增。这些结果表明,PF 可能通过抑制 DC 成熟和限制其刺激 T 细胞反应的能力,在体外有效预防和治疗 ACD 及其他炎症反应。

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