Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via Jak3/Stat3 signaling pathway

Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via Jak3/Stat3 signaling pathway
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Astilbin 通过 Jak3/Stat3 信号通路抑制 Th17 细胞分化并改善 BALB/c 小鼠中咪喹莫特诱导的银屑病样皮肤病变

DOI:
10.1016/j.intimp.2015.12.035
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发表时间:
2016-03-01
影响因子:
5.6
通讯作者:
Li, Ping
Li, Ping
中科院分区:
医学2区
文献类型:
--
作者:
Di, Ting-Ting;Ruan, Zhi-Tong;Li, Ping

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落新妇苷是从土茯苓根茎中提取的主要活性成分,在我国已被广泛用于治疗炎症和自身免疫性疾病。银屑病是一种常见的慢性炎症性疾病,其中辅助性T细胞17(Th 17)发挥重要作用,引起炎症反应。我们采用咪喹莫特(IMQ)诱导的银屑病样小鼠模型来研究落新妇苷在炎症中的作用。给小鼠施用25至50 mg/kg落新妇苷。通过组织学评估银屑病样病变的炎症,通过流式细胞术评估T细胞的循环水平,通过基于珠的免疫测定评估细胞因子。通过Western印迹法评估分离的T细胞中的Jak/Stat 3,通过RT-PCR评估ROR γ t表达。落新妇苷的施用改善了MQ诱导的角质形成细胞增殖、CD 3+细胞向银屑病病变的浸润,并改善了循环CD 4+和CD 8 + T细胞和炎性细胞因子(IL-17 A、TNF-α、IL-6、IFN-γ和IL-2)的升高。落新妇苷在体外抑制Th 17细胞分化和分离的T细胞IL-17分泌,抑制Th 17细胞中的Jak/Stat 3信号,同时上调银屑病皮损中Stat 3抑制剂SCOSE 3的表达。因此,落新妇苷可能通过抑制Th 17相关炎症来减轻银屑病样皮肤病变。落新妇苷是一种有意义的银屑病免疫调节药物。(C)2016作者由爱思唯尔公司出版
The flavonoid astilbin is the major active component extracted from the rhizome of Smilax glabra, which has been widely used in China to treat inflammatory and autoimmune diseases, Psoriasis is a common chronic inflammatory disease in which T helper 17 (Th17) cells play an important role, provoking inflammation. We employed an imiquimod (IMQ)-induced psoriasis-like mouse model to investigate the effect of astilbin in inflammation. Mice were administered 25 to 50 mg/kg astilbin. Inflammation of psoriasis-like lesions was assessed by histology, circulating levels of T cells were assessed by flow cytometry and cytoldnes by bead-based immunoassay. Jak/Stat3 in isolated T cells was assessed by Western blotting and ROR gamma t expression was assessed by RT-PCR Administration of astilbin ameliorated IMQ-induced keratinocyte proliferation, infiltration of CD3+ cells to psoriatic lesions and ameliorated elevations in circulating CD4+ and CD8+ T cells and inflammatory cytokines (IL-17A, TNF-alpha, IL-6, IFN-gamma and IL-2). In vitro, astilbin inhibited Th17 cell differentiation and IL-17 secretion of isolated T cells, and inhibited Jak/Stat3 signaling in Th17 cells, while up-regulating Stat3 inhibitor SCOSE3 expression in psoriatic lesions. Thus, astilbin likely alleviates psoriasis-like skin lesions by inhibiting Th17 related inflammation. Astilbin represents as an interesting candidate drug for immunoregulation of psoriasis. (C) 2016 The Authors. Published by Elsevier B.V.