title: 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.affiliation: Department of Genetic, Biology and Biochemistry, University of Torino, Italy. miriamcanavese@yahoo.com
authors.forename: M
authors.initials: M
authors.lastname: Canavese
authors.forename: F
authors.initials: F
authors.lastname: Altruda
authors.forename: L
authors.initials: L
authors.lastname: Silengo
authors.forename: V
authors.initials: V
authors.lastname: Castiglioni
authors.forename: E
authors.initials: E
authors.lastname: Scanziani
authors.forename: E
authors.initials: E
authors.lastname: Radaelli
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004431:Ear, External / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000235:genetics* / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology; D011565:Psoriasis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D012867:Skin / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000502:physiology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D053547:Keratin-14; D042461:Vascular Endothelial Growth Factor A