Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-7-28
pubmed:abstractText
Psoriasis is a common chronic inflammatory skin disease, characterized by epidermal hyperplasia, immune cell infiltration, increased dermal angiogenesis and local up-regulation of a variety of inflammatory mediators. Psoriasis is thought to be driven primarily by CD4(+) T cells with a T(h)1 and/or T(h)17 phenotype. Transgenic keratin 14 (K14)/vascular endothelial growth factor (VEGF) mice have previously been reported to develop a psoriasis-like phenotype. The aim of this study was to further characterize the model for validation as an in vivo screening model of psoriasis. Inflammation was induced in the ear skin with five topical applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and a significantly increased inflammation was found in TPA-induced K14/VEGF transgenic animals compared with wild-type mice. The amount of VEGF in the ear tissue was significantly elevated resulting in increased dermal angiogenesis. Furthermore, intense epidermal hyperplasia, CD3(+) infiltration and significantly increased amounts of (TNF) tumor necrosis factor alpha, IL-1 beta, IL-6, IL-12/23p40, IL-12p70, IL-22 and IL-17 were detected in the inflamed ear skin. This cytokine profile strongly suggests a T(h)17-mediated inflammation. All findings were a result of induced over-expression of VEGF. Topical treatment with betamethasone-17-valerate (BMS) significantly reduced ear skin inflammation and epidermal hyperplasia and also decreased the CD3(+) infiltration. In conclusion, the TPA-induced phenotype in K14/VEGF animals displayed several features of psoriasis, including a T(h)17 cytokine profile and a chronic-like progression, and can be used as an in vivo screening model of psoriasis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1460-2377
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1097-106
pubmed:meshHeading
pubmed-meshheading:18579711-Animals, pubmed-meshheading:18579711-Anti-Inflammatory Agents, pubmed-meshheading:18579711-Betamethasone 17-Valerate, pubmed-meshheading:18579711-Disease Models, Animal, pubmed-meshheading:18579711-Focal Epithelial Hyperplasia, pubmed-meshheading:18579711-Interleukin-17, pubmed-meshheading:18579711-Keratin-14, pubmed-meshheading:18579711-Lymphocyte Activation, pubmed-meshheading:18579711-Mice, pubmed-meshheading:18579711-Mice, Transgenic, pubmed-meshheading:18579711-Neovascularization, Pathologic, pubmed-meshheading:18579711-Otitis, pubmed-meshheading:18579711-Phorbol Esters, pubmed-meshheading:18579711-Psoriasis, pubmed-meshheading:18579711-Skin, pubmed-meshheading:18579711-T-Lymphocytes, Helper-Inducer, pubmed-meshheading:18579711-Vascular Endothelial Growth Factor A
pubmed:year
2008
pubmed:articleTitle
TPA induction leads to a Th17-like response in transgenic K14/VEGF mice: a novel in vivo screening model of psoriasis.
pubmed:affiliation
Section of Dermatology, Department of Pharmacology, LEO Pharma A/S, Industriparken 55, 2750 Ballerup, Denmark.
pubmed:publicationType
Journal Article