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.