The Expression and Regulation of Chemerin in the Epidermis

被引:59
作者
Banas, Magdalena [1 ]
Zegar, Aneta [1 ]
Kwitniewski, Mateusz [1 ]
Zabieglo, Katarzyna [1 ]
Marczynska, Joanna [1 ]
Kapinska-Mrowiecka, Monika [2 ]
LaJevic, Melissa [3 ,4 ]
Zabel, Brian A. [4 ]
Cichy, Joanna [1 ]
机构
[1] Jagiellonian Univ, Dept Immunol, Fac Biochem Biophys & Biotechnol, Krakow, Poland
[2] Zeromski Hosp, Dept Dermatol, Krakow, Poland
[3] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
[4] VA Palo Alto Hlth Care Syst, Palo Alto Vet Inst Res, Palo Alto, CA USA
基金
美国国家卫生研究院;
关键词
SKIN INFLAMMATION; ONCOSTATIN-M; EPITHELIAL-CELLS; HUMAN KERATINOCYTES; ENDOTHELIAL-CELLS; GENE-EXPRESSION; DENDRITIC CELLS; RECEPTOR CCRL2; DISEASED SKIN; MESSENGER-RNA;
D O I
10.1371/journal.pone.0117830
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-1 beta. 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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页数:19
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