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.
Clinical, pathological and immunological features of psoriatic-like lesions affecting keratin 14-vascular endothelial growth factor transgenic mice / M. Canavese, F. Altruda, L. Silengo, V. Castiglioni, E. Scanziani, E. Radaelli. - In: HISTOLOGY AND HISTOPATHOLOGY. - ISSN 0213-3911. - 26:3(2011 Mar), pp. 285-296.
|Titolo:||Clinical, pathological and immunological features of psoriatic-like lesions affecting keratin 14-vascular endothelial growth factor transgenic mice|
SCANZIANI, EUGENIO (Penultimo)
RADAELLI, ENRICO (Ultimo)
|Parole Chiave:||Angiogenesis; VEGF; Disease animal models; Psoriasis; Skin|
|Settore Scientifico Disciplinare:||Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria|
|Data di pubblicazione:||mar-2011|
|Appare nelle tipologie:||01 - Articolo su periodico|