Publication: Clinical, pathological and immunological features of psoriatic-like lesions affecting keratin 14-vascular endothelial growth factor transgenic mice
Authors
Canavese, M. ; Altruda, F. ; Silengo, L. ; Castiglioni, V. ; Scanziani, E. ; Radaelli, E.
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Publisher
Murcia: F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
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.
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