Clinical, pathological and immunological features of psoriatic-like lesions affecting keratin 14-vascular endothelial growth factor transgenic mice.

Abstract

Up-regulation of vascular endothelial growth factor (VEGF) plays a primary role in the pathogenesis of psoriasis. Transgenic mice over-expressing VEGF under the Keratin 14 (K14) promoter develop an inflammatory skin condition with many of the pathobiological features of human psoriasis. In this work, the development of spontaneous psoriatic-like dermatitis in K14-VEGF transgenic mice was monitored from week 6 to week 44 and skin lesions were characterized clinically (application of a clinical score system comparable to the human Psoriasis Area and Severity Index), microscopically (histopathology, leukocyte subset and neoangiogensis) and immunologically (evaluation of local and systemic cytokine/chemokine profiles). Based on PASI score system, three progressive clinical phases were identified: mild acute (8-14 weeks of age), moderate subacute (15-21 weeks of age) and severe chronic-active (22-44 weeks of age) dermatitis. Microscopically, skin lesions consisted of progressive proliferative psoriatic-like dermatitis dominated by dermo-epidermal infiltrates of CD3-positive lymphocytes, an increased number of mast cells and neoangiogenesis. Both local and systemic up-regulation of pro-inflammatory (IL-12, TNF-alpha, IL-6, MCP-1 and IL-8) and regulatory (IL-10) cytokines/chemokines was observed, mainly during the later stages of disease development. The results obtained in this study further confirm the central role of VEGF over-expression in the development of psoriatic-like dermatitis. Similarly to what is reported for human psoriasis, both the local and systemic immunologic profiles observed in K14-VEGF transgenic mice suggest that a combined Th1 and Th17 response may be implicated in lesion development. The identification of three progressive stages of disease, each with peculiar clinicopathological features, renders the K14-VEGF transgenic mouse a valuable model to study novel immunotherapies for psoriasis.

• Authors: M Canavese, F Altruda, L Silengo, V Castiglioni, E Scanziani, E Radaelli
• Journal: Histology and histopathology (Histol Histopathol) Vol. 26 Issue 3 Pg. 285-96 (03 2011) ISSN: 1699-5848 [Electronic] Spain
• PMID: 21210341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Cytokines
• Keratin-14
• Vascular Endothelial Growth Factor A

Topics

• Aging (metabolism, physiology)
• Animals
• Chemokines (metabolism)
• Cytokines (metabolism)
• Ear, External (pathology)
• Female
• Immunohistochemistry
• Keratin-14 (genetics, physiology)
• Lymphocyte Subsets (physiology)
• Male
• Mice
• Mice, Transgenic
• Neovascularization, Pathologic (pathology)
• Psoriasis (genetics, immunology, pathology)
• Skin (pathology)
• Vascular Endothelial Growth Factor A (genetics, physiology)