The efficacy of in vivo administration of Apremilast on mesenchymal stem cells derived from psoriatic patients

被引:9
作者
Campanati, Anna [1 ]
Caffarini, Miriam [2 ]
Diotallevi, Federico [1 ]
Radi, Giulia [1 ]
Lucarini, Guendalina [2 ]
Di Vincenzo, Mariangela [2 ]
Orciani, Monia [2 ]
Offidani, Annamaria [1 ]
机构
[1] Univ Politecn Marche, Dermatol Clin, Dept Clin & Mol Sci, Ancona, Italy
[2] Univ Politecn Marche, Dept Clin & Mol Sci, Histol, Via Tronto 10-A, I-60126 Ancona, Italy
关键词
Psoriasis; Apremilast; IDO; Inflammation; iNOS; MSCs; VEGF; NITRIC-OXIDE; INDOLEAMINE 2,3-DIOXYGENASE; KYNURENINE PATHWAY; ATOPIC-DERMATITIS; EXPRESSION; IMBALANCE; VEGF; ANGIOGENESIS; FIBROBLASTS; ETANERCEPT;
D O I
10.1007/s00011-020-01412-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:79 / 87
页数:9
相关论文
共 32 条
[1]   Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts [J].
Asp, Linnea ;
Johansson, Anne-Sofie ;
Mann, Amandeep ;
Owe-Larsson, Bjorn ;
Urbanska, Ewa M. ;
Kocki, Tomasz ;
Kegel, Magdalena ;
Engberg, Goran ;
Lundkvist, Gabriella B. S. ;
Karlsson, Hakan .
JOURNAL OF INFLAMMATION-LONDON, 2011, 8
[2]   Nitric oxide function in the skin [J].
Cals-Grierson, MM ;
Ormerod, AD .
NITRIC OXIDE-BIOLOGY AND CHEMISTRY, 2004, 10 (04) :179-193
[3]   Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells [J].
Campanati, A. ;
Orciani, M. ;
Sorgentoni, G. ;
Consales, V. ;
Mattioli Belmonte, M. ;
Di Primio, R. ;
Offidani, A. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2018, 193 (02) :234-240
[4]   Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1-Th17/Th2 imbalance of psoriasis [J].
Campanati, A. ;
Orciani, M. ;
Consales, V. ;
Lazzarini, R. ;
Ganzetti, G. ;
Di Benedetto, G. ;
Di Primio, R. ;
Offidani, A. .
ARCHIVES OF DERMATOLOGICAL RESEARCH, 2014, 306 (10) :915-920
[5]   Effect of biologic therapies targeting tumour necrosis factor-α on cutaneous mesenchymal stem cells in psoriasis [J].
Campanati, A. ;
Orciani, M. ;
Gorbi, S. ;
Regoli, F. ;
Di Primio, R. ;
Offidani, A. .
BRITISH JOURNAL OF DERMATOLOGY, 2012, 167 (01) :68-76
[6]   Pathogenetic Characteristics of Mesenchymal Stem Cells in Hidradenitis Suppurativa [J].
Campanati, Anna ;
Orciani, Monia ;
Sorgentoni, Giulia ;
Consales, Veronica ;
Offidani, Annamaria ;
Di Primio, Roberto .
JAMA DERMATOLOGY, 2018, 154 (10) :1184-1190
[7]   TNF-α inhibitors reduce the pathological Th1-Th17/Th2 imbalance in cutaneous mesenchymal stem cells of psoriasis patients [J].
Campanati, Anna ;
Orciani, Monia ;
Lazzarini, Raffaella ;
Ganzetti, Giulia ;
Consales, Veronica ;
Sorgentoni, Giulia ;
Di Primio, Roberto ;
Offidani, Annamaria .
EXPERIMENTAL DERMATOLOGY, 2017, 26 (04) :319-324
[8]   The effect of etanercept on vascular endothelial growth factor production by cutaneous mesenchymal stem cells from patients with psoriasis [J].
Campanati, Anna ;
Orciani, Monia ;
Ganzetti, Giulia ;
Consales, Veronica ;
Di Primio, Roberto ;
Offidani, Annamaria .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2016, 44 :6-9
[9]   Mesenchymal stem cells, fibroblasts and pericytes: Different functional states of the same cell? [J].
Covas, DT ;
Penepucci, RA ;
Fontes, AM ;
Orellana, M ;
Prata, KL ;
Neder, L ;
Perez, LC ;
Carrara, RC ;
Araujo, AG ;
Zago, MA .
BLOOD, 2005, 106 (11) :157B-157B
[10]   Indoleamine 2,3 Dioxygenase-Mediated Tryptophan Catabolism Regulates Accumulation of Th1/Th17 Cells in the Joint in Collagen-Induced Arthritis [J].
Criado, Gabriel ;
Simelyte, Egle ;
Inglis, Julia J. ;
Essex, David ;
Williams, Richard O. .
ARTHRITIS AND RHEUMATISM, 2009, 60 (05) :1342-1351