Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice by inhibiting the maturation and activation of dendritic cells.
Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice by inhibiting the maturation and activation of dendritic cells.
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丹皮酚通过抑制树突状细胞的成熟和活化改善 BALB/c 小鼠中咪喹莫特诱导的银屑病样皮肤病变
DOI：
10.3892/ijmm.2017.2930
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发表时间：
2017-05
影响因子：
5.4
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Meng Y;Wang M;Xie X;Di T;Zhao J;Lin Y;Xu X;Li N;Zhai Y;Wang Y;Li P
丹皮酚是一种从中药牡丹皮中提取的活性成分，具有抗炎、镇痛、抗氧化和抗过敏的特性。银屑病是一种慢性、复发性、炎症性皮肤病，伴有树突状细胞（dc）中toll样受体（TLRs）的过度激活，其主要负责启动免疫反应。我们研究了丹皮酚对咪喹莫特（IMQ）诱导的牛皮癣样小鼠模型和R848刺激的小鼠骨髓源性树突状细胞（bmdc）炎症的影响。小鼠分别灌胃100 mg/kg（高）、50 mg/kg（中）和25 mg/kg（低）丹皮酚。我们通过组织学变化、免疫印迹法检测皮肤病变中髓样分化因子88 （MyD88）和TLR8蛋白水平、免疫测定法检测皮肤中CD11c+ DCs水平和流式细胞术检测脾脏中CD11c+ DCs水平来评估银屑病样病变的炎症。采用RT-PCR和ELISA检测皮肤病变和BMDCs的炎症因子[白细胞介素(IL)-23、IL-12和IL-1β]。丹皮酚的应用降低了imq诱导的角质细胞增殖和CD3+细胞的浸润，同时改善了脾脏和皮肤中的CD11c+细胞，降低了皮肤病变中的MyD88和TLR8蛋白。丹皮酚抑制imq诱导的BMDCs中IL-23 mRNA的表达，但不抑制IL-12和IL-1β的表达，同时显著降低体外表达MHCII、CD80和CD86的dc的水平。这些结果表明，丹皮酚通过降低TLR7/8信号通路中的MyD88和TLR8蛋白抑制DCs的成熟和激活，最终缓解牛皮癣样皮肤病变。dc中的TLR7/8信号通路为银屑病的发病机制提供了重要线索，丹皮酚可能是治疗银屑病的有效药物。
Paeonol, an active component derived from the traditional Chinese medicine Cortex Moutan, possesses anti-inflammatory, analgesic, antioxidant and anti-allergic properties. Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of Toll-like receptors (TLRs) in dendritic cells (DCs), which are primarily responsible for initiating an immune response. We investigated the effect of paeonol on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by R848. Mice were intragastrically administered 100 mg/kg (high), 50 mg/kg (medium) and 25 mg/kg (low) paeonol, respectively. We evaluated inflammation of psoriasis-like lesions based on histological changes, protein levels of myeloid differentiation factor 88 (MyD88) and TLR8 in skin lesions by western blotting, and levels of CD11c+ DCs in skin by immunoassay and in spleens by flow cytometry. Inflammatory cytokines [interleukin (IL)-23, IL-12 and IL-1β] in skin lesions and BMDCs were also assessed by RT-PCR and ELISA. Application of paeonol decreased IMQ-induced keratinocyte proliferation, and infiltration of CD3+ cells, while the treatment ameliorated CD11c+ cells in the spleen and skin, and reduced MyD88 and TLR8 proteins in skin lesions. Paeonol inhibited IMQ-induced mRNA expression of IL-23, but not IL-12 and IL-1β in BMDCs, along with significantly lower levels of DCs expressing MHCII, CD80 and CD86 in vitro. These results indicate that paeonol suppresses the maturation and activation of DCs by decreasing MyD88 and TLR8 proteins in the TLR7/8 signaling pathway which finally alleviates psoriasis-like skin lesions. The TLR7/8 signaling pathway in DCs provides an important insight into the mechanism of psoriasis, and paeonol may be a potent therapeutic drug for psoriasis.