Fibroblasts to Keratinocytes Redox Signaling: The Possible Role of ROS in Psoriatic Plaque Formation

Antioxidants

Claudia Fiorillo¹  Matteo Becatti¹  Niccolò Taddei¹  Victoria Barygina¹  Francesca Prignano²  Torello Lotti³ 

[1] Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, viale Morgagni 50, 50134 Florence, Italy;Department of Dermatological Sciences, University of Florence, Villa Basilewsky, via Lorenzo Il Magnifico 104, 50129 Florence, Italy;Department of Nuclear, Subnuclear and Radiation Physics, Via Plinio 44, 00193 Rome, Italy;

关键词: nox4;    psoriasis;    ros signalling;    fibroblasts;    keratinocytes;    co-culture;    redox;    nadph oxidase;   

DOI  :  10.3390/antiox8110566

来源: DOAJ

【 摘 要 】

Although the role of reactive oxygen species-mediated (ROS-mediated) signalling in physiologic and pathologic skin conditions has been proven, no data exist on the skin cells ROS-mediated communication. Primary fibroblasts were obtained from lesional and non-lesional skin of psoriatic patients. ROS, superoxide anion, calcium and nitric oxide levels and lipoperoxidation markers and total antioxidant content were measured in fibroblasts. NADPH oxidase activity and NOX1, 2 and 4 expressions were assayed and NOX4 silencing was performed. Fibroblasts and healthy keratinocytes co-culture was performed. MAPK pathways activation was studied in fibroblasts and in co-cultured healthy keratinocytes. Increased intracellular calcium, •NO and ROS levels as well as an enhanced NADPH oxidase 4 (NOX4)−mediated extracellular ROS release was shown in lesional psoriatic vs. control fibroblasts. Upon co-culture with lesional fibroblasts, keratinocytes showed p38 and ERK MAPKs pathways activation, ROS, Ca²⁺ and •NO increase and cell cycle acceleration. Notably, NOX4 knockdown significantly reduced the observed effects of lesional fibroblasts on keratinocyte cell cycle progression. Co-culture with non-lesional psoriatic and control fibroblasts induced slight cell cycle acceleration, but notable intracellular ROS accumulation and ERK MAPK activation in keratinocytes. Collectively, our data demonstrate that NOX4 expressed in dermal fibroblasts is essential for the redox paracrine regulation of epidermal keratinocytes proliferation.

【 授权许可】

Unknown