Expression of the vanin gene family in normal and inflamed human skin: Induction by proinflammatory cytokines

Patrick A.M. Jansen, Marijke Kamsteeg, Diana Rodijk-Olthuis, Ivonne M.J.J. Van Vlijmen-Willems, Gys J. De Jongh, Mieke Bergers, Geuranne S. Tjabringa, Patrick L.J.M. Zeeuwen, Joost Schalkwijk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2167-2174
Number of pages8
JournalJournal of Investigative Dermatology
Volume129
Issue number9
DOIs
Publication statusPublished - Sep 2009
Externally publishedYes

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