Expression of the Vanin Gene Family in Normal and Inflamed Human Skin: Induction by Proinflammatory Cytokines

被引:69
作者
Jansen, Patrick A. M. [1 ,2 ]
Kamsteeg, Marijke [1 ,2 ]
Rodijk-Olthuis, Diana [1 ,2 ]
van Vlijmen-Willems, Ivonne M. J. J. [1 ,2 ]
de Jongh, Gys J. [1 ,2 ]
Bergers, Mieke [1 ,2 ]
Tjabringa, Geuranne S. [1 ,2 ]
Zeeuwen, Patrick L. J. M. [1 ,2 ]
Schalkwijk, Joost [1 ,2 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Dermatol, NL-6525 ED Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6525 ED Nijmegen, Netherlands
关键词
ACTIVATED-RECEPTOR-GAMMA; HUMAN EPIDERMAL-KERATINOCYTES; ATOPIC-DERMATITIS; TRANSGLUTAMINASE ACTIVITY; PSORIATIC SKIN; DIFFERENTIATION; PANTETHEINASE; DISEASE; MOUSE; LOCALIZATION;
D O I
10.1038/jid.2009.67
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
The vanin gene family encodes secreted and membrane-bound ectoenzymes that convert pantetheine into pantothenic acid and cysteamine. Recent studies in a mouse colitis model indicated that vanin-1 has proinflammatory activity and suggest that pantetheinases are potential therapeutic targets in inflammatory diseases. In a microarray analysis of epidermal gene expression of psoriasis and atopic dermatitis lesions, we identified vanin-3 as the gene showing the highest differential expression of all annotated genes that we studied (19-fold upregulation in psoriasis). Quantitative real-time PCR analysis confirmed the microarray data on vanin-3 and showed similar induction of vanin-1, but not of vanin-2, in psoriatic epidermis. Immunohistochemistry showed that vanin-3 is expressed in the differentiated epidermal layers. Using submerged and organotypic keratinocyte cultures, we found that vanin-1 and vanin-3 are induced at the mRNA and protein level by psoriasis-associated proinflammatory cytokines (Th17/Th1) but not by Th2 cytokines. We hypothesize that increased levels of pantetheinase activity are part of the inflammatory-regenerative epidermal differentiation program, and may contribute to the phenotype observed in psoriasis.
引用
收藏
页码:2167 / 2174
页数:8
相关论文
共 51 条
[1]   Vanin-1, a novel GPI-linked perivascular molecule involved in thymus homing [J].
AurrandLions, M ;
Galland, F ;
Bazin, H ;
Zakharyev, VM ;
Imhof, BA ;
Naquet, P .
IMMUNITY, 1996, 5 (05) :391-405
[2]   PRECOCIOUS APPEARANCE OF INVOLUCRIN AND EPIDERMAL TRANSGLUTAMINASE DURING DIFFERENTIATION OF PSORIATIC SKIN [J].
BERNARD, BA ;
REANO, A ;
DARMON, YM ;
THIVOLET, J .
BRITISH JOURNAL OF DERMATOLOGY, 1986, 114 (03) :279-283
[3]   Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor γ activity [J].
Berruyer, Carole ;
Pouyet, Laurent ;
Millet, Virginie ;
Martin, Florent M. ;
LeGoffic, Aude ;
Canonici, Alexandra ;
Garcia, Stephane ;
Bagnis, Claude ;
Naquet, Philippe ;
Galland, Franck .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (13) :2817-2827
[4]   Treatment of active psoriatic arthritis with the PPARγ ligand pioglitazone:: an open-label pilot study [J].
Bongartz, T ;
Coras, B ;
Vogt, T ;
Schölmerich, J ;
Müller-Ladner, U .
RHEUMATOLOGY, 2005, 44 (01) :126-129
[5]   The cornified envelope: A model of cell death in the skin [J].
Candi, E ;
Schmidt, R ;
Melino, G .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (04) :328-340
[6]   Expression of transglutaminase 5 in normal and pathologic human epidermis [J].
Candi, E ;
Oddi, S ;
Paradisi, A ;
Terrinoni, A ;
Ranalli, M ;
Teofoli, P ;
Citro, G ;
Scarpato, S ;
Puddu, P ;
Melino, G .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 119 (03) :670-677
[7]   High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis [J].
de Jongh, GJ ;
Zeeuwen, PLJM ;
Kucharekova, M ;
Pfundt, R ;
van der Valk, PG ;
Blokx, W ;
Dogan, A ;
Hiemstra, PS ;
van de Kerkhof, PC ;
Schalkwijk, J .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2005, 125 (06) :1163-1173
[8]   Topical treatment with thiazolidinediones, activators of peroxisome proliferator-activated receptor-γ, normalizes epidermal homeostasis in a murine hyperproliferative disease model [J].
Demerjian, M ;
Man, MQ ;
Choi, EH ;
Brown, BE ;
Crumrine, D ;
Chang, S ;
Mauro, T ;
Elias, PM ;
Feingold, KR .
EXPERIMENTAL DERMATOLOGY, 2006, 15 (03) :154-160
[9]   Stratum corneum defensive functions: An integrated view [J].
Elias, PM .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2005, 125 (02) :183-200
[10]   Troglitazone improves psoriasis and normalizes models of proliferative skin disease -: Ligands for peroxisome proliferator-activated receptor-γ inhibit keratinocyte proliferation [J].
Ellis, CN ;
Varani, J ;
Fisher, GJ ;
Zeigler, ME ;
Pershadsingh, HA ;
Benson, SC ;
Chi, YQ ;
Kurtz, TW .
ARCHIVES OF DERMATOLOGY, 2000, 136 (05) :609-616