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Title: Ex vivo culture of lesional psoriasis skin for pharmacological testing
Author: Tiirikainen, Minna Lund
Woetmann, Anders
Norsgaard, Hanne
Santamaria Babí, Luis F.
Lovato, Paola
Keywords: Psoriasi
Issue Date: 27-Dec-2019
Publisher: Elsevier
Abstract: Background: Psoriasis is a chronic, inflammatory skin disorder resulting from a complex interplay between immune and skin cells via release of soluble mediators. While a lot is known about the molecular mechanisms behind psoriasis pathogenesis, there is still a need for preclinical research models that accuratelyreplicate the disease. Objective: This study aimed to develop and characterize ex vivo culture of psoriasis skin as a model for pharmacological testing, where the immunological events of psoriasis can be followed. Methods: Full thickness punch biopsies of lesional psoriasis skin were cultured in submerged conditions up to 144 h followingin situ T cell stimulation with rhIL-23 and anti-CD3 and anti-CD28 antibodies. The Tcell mediated skin inflammation was assessed by gene and protein l analysis for a panel of inflammatory mediators. Tissue integrity and morphology were evaluated by histological analysis. Results: T cell stimulation resulted in functional and psoriasis specificin situ activation of T cells. The expression levels of most of the proinflammatory mediators related to both immune and skin cells were comparable to these in freshly isolated tissue at 48 and 96 h of culture. Tissue integrity and morphology were sustained up to 96 h. Treatment with a corticosteroid reduced the expression of several proinflammatory cytokines and chemokines, whereas anti-IL-17A antibody treatment reduced the expression of the IL-17A downstream markers IL-8 and DEFB4. Conclusion: By preserving keyimmunopathological mechanisms of psoriasis, ex vivo culture of psoriasis skin can be used for the investigation of inflammatory processes of psoriasis and for preclinical drug discovery research.
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It is part of: Journal of Dermatological Science, 2019, vol. 97, num. 2, p. 109-116
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ISSN: 0923-1811
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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