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CKLF1 的 C 端肽 C19 可减少银屑病皮肤毛细血管的炎症和增殖。

C19, a C-terminal peptide of CKLF1, decreases inflammation and proliferation of dermal capillaries in psoriasis.

机构信息

Department of Dermatology, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China.

出版信息

Sci Rep. 2017 Oct 24;7(1):13890. doi: 10.1038/s41598-017-13799-x.

DOI:10.1038/s41598-017-13799-x
PMID:29066845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5655640/
Abstract

Psoriasis is a chronic inflammatory autoimmune disease with undefined etiology. Chemokine-like factor 1 (CKLF1), a human cytokine that is a functional ligand for CCR4, displays chemotactic activities in a wide spectrum of leukocytes and plays an important role in psoriasis development. In previous study, our laboratory found that the expression of CKLF1 increased in psoriatic lesions. C19 as a CKLF1's C-terminal peptide has been reported to exert inhibitory effects on a variety of diseases. However, the protective roles of C19 in endothelial cells proliferation and inflammatory cells chemotaxis remain elusive in psoriasis. In this study we examined the protective effect of C19 on both the cellular model and the animal model. The effects of C19 on endothelial cells proliferation and inflammatory cells chemotaxis were investigated in cultured human umbilical vein endothelial cells (HUVECs) and imiquimod-induced psoriasiform inflammation of BALB/c mice based on techniques including immunohistochemical analysis, quantitative real-time PCR (qRT-PCR), western blot, transwell, and EdU assay. This study shows that CKLF1-C19 significantly protects against psoriasis by inhibiting the infiltration of inflammatory cells and proliferation of microvascular cells, possibly via inhibiting MAPK pathways.

摘要

银屑病是一种病因不明的慢性炎症性自身免疫性疾病。趋化因子样因子 1(CKLF1)是一种人类细胞因子,作为 CCR4 的功能性配体,对广泛的白细胞具有趋化活性,并在银屑病的发展中发挥重要作用。在之前的研究中,我们的实验室发现 CKLF1 的表达在银屑病皮损中增加。C19 作为 CKLF1 的 C 端肽已被报道对多种疾病具有抑制作用。然而,C19 在血管内皮细胞增殖和炎症细胞趋化中的保护作用在银屑病中仍不清楚。在这项研究中,我们检查了 C19 对细胞模型和动物模型的保护作用。基于免疫组织化学分析、实时定量 PCR(qRT-PCR)、western blot、transwell 和 EdU 测定等技术,研究了 C19 对培养的人脐静脉内皮细胞(HUVECs)和咪喹莫特诱导的 BALB/c 小鼠银屑病样炎症中内皮细胞增殖和炎症细胞趋化的影响。本研究表明,CKLF1-C19 通过抑制炎症细胞浸润和微血管细胞增殖,显著抑制银屑病,可能通过抑制 MAPK 通路。

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Chemokine-like factor 1-derived C-terminal peptides induce the proliferation of dermal microvascular endothelial cells in psoriasis.
CKLF1干扰通过CCR5减轻白细胞介素-1β诱导的软骨细胞炎症、凋亡和细胞外基质降解。
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趋化因子样因子1衍生的C末端肽可诱导银屑病中真皮微血管内皮细胞的增殖。
PLoS One. 2015 Apr 27;10(4):e0125073. doi: 10.1371/journal.pone.0125073. eCollection 2015.
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Use of biologic agents in combination with other therapies for the treatment of psoriasis.生物制剂与其他疗法联合用于治疗银屑病。
Am J Clin Dermatol. 2014 Dec;15(6):467-78. doi: 10.1007/s40257-014-0097-1.
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