title: Expression of the vanin gene family in normal and inflamed human skin: induction by proinflammatory cytokines.
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.
authors.affiliation: Department of Dermatology and Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Patrick A M
authors.initials: PA
authors.lastname: Jansen
authors.forename: Marijke
authors.initials: M
authors.lastname: Kamsteeg
authors.forename: Diana
authors.initials: D
authors.lastname: Rodijk-Olthuis
authors.forename: Ivonne M J J
authors.initials: IM
authors.lastname: van Vlijmen-Willems
authors.forename: Gys J
authors.initials: GJ
authors.lastname: de Jongh
authors.forename: Mieke
authors.initials: M
authors.lastname: Bergers
authors.forename: Geuranne S
authors.initials: GS
authors.lastname: Tjabringa
authors.forename: Patrick L J M
authors.initials: PL
authors.lastname: Zeeuwen
authors.forename: Joost
authors.initials: J
authors.lastname: Schalkwijk