The efficacy of in vivo administration of Apremilast on mesenchymal stem cells derived from psoriatic patients
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Inflammation Research
ORIGINAL RESEARCH PAPER
The efficacy of in vivo administration of Apremilast on mesenchymal stem cells derived from psoriatic patients Anna Campanati1 · Miriam Caffarini2 · Federico Diotallevi1 · Giulia Radi1 · Guendalina Lucarini2 · Mariangela Di Vincenzo2 · Monia Orciani2 · Annamaria Offidani1 Received: 24 July 2020 / Revised: 2 October 2020 / Accepted: 6 October 2020 © Springer Nature Switzerland AG 2020
Abstract Introduction Psoriasis cellular hallmarks, such as the imbalance between Th1/Th17 and Th2 cytokines and the dysregulated expression of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase, (iNOS) and indoleamine 2,3-dioxygenase (IDO), are all detectable in mesenchymal stem cells (MSCs) suggesting that psoriasis originates at mesenchymal level. Aim of the study: In this scenario, MSCs may become the new therapeutic target and interest in the effects of traditionally used drugs, such as Apremilast, on MSCs has greatly increased. Materials and Methods MSCs from control subjects (C-MSCs) and from psoriatic patients before (PsO MSCs T0) and after in vivo treatment with Apremilast (PsO-MSCs T12) were isolated and characterized; subsequently, the effects of Apremilast on VEGF, iNOS and IDO expression were evaluated by immunocytochemistry (ICC). The expression of VEGF, iNOS and IDO was also detected in skin sections by immunohistochemistry (IHC). Results The results indicate that in vivo administration of Apremilast is able to drive the altered profile of PsO-MSCs towards a more physiological pattern. In skin sections, the role of Apremilast is evident in reducing VEGF, iNOS and IDO expression. Conclusion Apremilast treatment influences the expression of VEGF, iNOS and IDO not only by keratinocytes but also by MSCs, restoring their intrinsic profile and their natural anti-inflammatory action, and decreasing the auto-inflammatory process that underpins the development of psoriasis. Keywords Psoriasis · Apremilast · IDO · Inflammation · iNOS · MSCs · VEGF
Introduction Psoriasis is a chronic inflammatory and immune-mediated disease, whose systemic involvement has been widely accepted. It is characterized by imbalance between the Th1Th17 and Th2 axes [1], over-expression of specific molecules (e.g. iNOS, VEGF) [2] and dysregulation of others, such as Indoleamine 2,3-dioxygenase (IDO) [3]. IDO acts Responsible Editor: J. Di Battista. * Monia Orciani [email protected] 1
Department of Clinical and Molecular Sciences, Dermatology Clinic, Università Politecnica delle Marche, Ancona, Italy
Department of Clinical and Molecular Sciences, Histology, Università Politecnica delle Marche, Via Tronto 10/A, 60126, Ancona, Italy
2
as an immunoregulatory enzyme capable of suppressing T‐cell responses; keratinocytes and fibroblasts upregulate IDO expression and activation in vitro in response to proinflammatory stimuli [4, 5]. It has already been demonstrated that immune cells from patients with psoriasis have a defect in upregulating IDO in response to inflammation
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