青蒿素，一种抑制酒渣鼻炎症和血管生成的潜在选择。
Artemisinin, a potential option to inhibit inflammation and angiogenesis in rosacea.
机构信息
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University, Changsha, Hunan, China; Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
出版信息
Biomed Pharmacother. 2019 Sep;117:109181. doi: 10.1016/j.biopha.2019.109181. Epub 2019 Jul 5.
BACKGROUND
Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and vascular system. Artemisinin (ART), an anti-malaria drug, was reported to have several effects including anti-inflammation and anti-angiogenesis activities. However, the role of ART on rosacea remains unclear.
OBJECTIVES
To investigate the effects and molecular mechanism of ART on rosacea.
METHOD
In rosacea-like mouse model, the phenotype of rosacea lesions was evaluated by redness score, the inflammatory biomarkers were analyzed by qPCR, and the infiltration of inflammatory cells were assessed by IHC analysis and immunofluorescence. In vitro, LL37-induced expression of inflammatory factors in HaCaT cells was detected by qPCR, potential signaling pathways were detected by Western blotting or immunofluorescence. Migration ability of human umbilical vein endothelial cells (HUVECs) was evaluated by cell scratch and transwell assays.
RESULT
The skin erythema and histopathological alteration, as well as the elevated pro-inflammatory factors (IL-1β, IL6, TNFα) and TLR2 were significantly ameliorated by ART treatment in LL37-induced rosacea-like mice. In addition, ART reduced the infiltration of CD4 T cells, macrophages and neutrophils, and repressed the expression of immune cells related chemokines (CXCL10, CCL20, CCL2 and CXCL2) in mouse lesions. In HaCaT cells, ART significantly decreased the LL37-induced expression of inflammatory biomarkers. Moreover, we found that ART inhibited rosacea-like inflammation via NF-kB signaling pathways in HaCaT cells. Finally, for vascular dysregulation, ART repressed the angiogenesis in mouse model and inhibited the LL37-induced HUVECs migration in vitro.
CONCLUSION
ART ameliorated rosacea-like dermatitis by regulating immune response and angiogenesis, indicating that it could represent an effective therapeutic option for patients with rosacea.
背景
酒渣鼻是一种面部慢性炎症性皮肤疾病，伴有免疫和血管系统功能障碍。青蒿素（ART）是一种抗疟药物，据报道具有多种作用，包括抗炎和抗血管生成作用。然而，ART 对酒渣鼻的作用尚不清楚。
目的
研究 ART 对酒渣鼻的作用及分子机制。
方法
在酒渣鼻样小鼠模型中，通过红斑评分评估酒渣鼻病变的表型，通过 qPCR 分析炎症生物标志物，通过免疫组化分析和免疫荧光评估炎症细胞的浸润。在体外，通过 qPCR 检测 LL37 诱导 HaCaT 细胞中炎症因子的表达，通过 Western blot 或免疫荧光检测潜在的信号通路。通过细胞划痕和 Transwell 实验评估人脐静脉内皮细胞（HUVEC）的迁移能力。
结果
ART 治疗可显著改善 LL37 诱导的酒渣鼻样小鼠的皮肤红斑和组织病理学改变，以及升高的促炎因子（IL-1β、IL6、TNFα）和 TLR2。此外，ART 减少了 CD4 T 细胞、巨噬细胞和中性粒细胞的浸润，并抑制了小鼠病变中免疫细胞相关趋化因子（CXCL10、CCL20、CCL2 和 CXCL2）的表达。在 HaCaT 细胞中，ART 显著降低了 LL37 诱导的炎症生物标志物的表达。此外，我们发现 ART 通过 NF-kB 信号通路抑制了 HaCaT 细胞中的酒渣鼻样炎症。最后，对于血管失调，ART 抑制了小鼠模型中的血管生成，并抑制了体外 LL37 诱导的 HUVEC 迁移。
结论
ART 通过调节免疫反应和血管生成改善酒渣鼻样皮炎，表明它可能是酒渣鼻患者的有效治疗选择。
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