The expression and regulation of chemerin in the epidermis.

The expression and regulation of chemerin in the epidermis.
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表皮凯莫瑞的表达和调控。

DOI:
10.1371/journal.pone.0117830
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Cichy J
Cichy J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Banas M;Zegar A;Kwitniewski M;Zabieglo K;Marczynska J;Kapinska-Mrowiecka M;LaJevic M;Zabel BA;Cichy J

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Chemerin是G蛋白偶联受体CMKLR 1的蛋白质配体,也与两种非典型七螺旋受体CCRL 2和GPR 1结合。Chemerin是一种白细胞引诱剂、脂肪因子和抗微生物蛋白。尽管chemerin最初被确定为健康皮肤角质形成细胞中高度表达的基因,在银屑病期间下调,但特定细胞因子和微生物因子对皮肤中chemerin及其受体的调节仍未得到探索。在这里,我们表明,chemerin,CMKLR 1,CCRL 2和GPR 1在人类和小鼠表皮中表达,这表明该组织可能是chemerin介导的作用的来源和靶点。在人类皮肤培养物中,chemerin被与银屑病有关的关键细胞因子IL-17和IL-22显著下调,而被急性期细胞因子制瘤素M和IL-1β上调。此外,我们表明,在体外的人角质形成细胞和小鼠皮肤在体内响应特定的微生物信号来调节chemerin及其受体的表达水平。此外,在皮肤感染模型中,chemerin是体内最大杀菌作用所需的。总之,我们的研究结果揭示了以前未表征的趋化蛋白在皮肤中表达的调节剂,并确定了趋化蛋白在皮肤屏障防御微生物病原体中的生理作用。
Chemerin is a protein ligand for the G protein-coupled receptor CMKLR1 and also binds to two atypical heptahelical receptors, CCRL2 and GPR1. Chemerin is a leukocyte attractant, adipokine, and antimicrobial protein. Although chemerin was initially identified as a highly expressed gene in healthy skin keratinocytes that was downregulated during psoriasis, the regulation of chemerin and its receptors in the skin by specific cytokines and microbial factors remains unexplored. Here we show that chemerin, CMKLR1, CCRL2 and GPR1 are expressed in human and mouse epidermis, suggesting that this tissue may be both a source and target for chemerin mediated effects. In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, key cytokines implicated in psoriasis, whereas it is upregulated by acute phase cytokines oncostatin M and IL-1β. Moreover, we show that human keratinocytes in vitro and mouse skin in vivo respond to specific microbial signals to regulate expression levels of chemerin and its receptors. Furthermore, in a cutaneous infection model, chemerin is required for maximal bactericidal effects in vivo. Together, our findings reveal previously uncharacterized regulators of chemerin expression in skin and identify a physiologic role for chemerin in skin barrier defense against microbial pathogens.
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影响因子: --
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发表时间: 1987-04-01
影响因子: 2.9
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