Acta Dermato-Venerelogica Issue No 7, 2017 97-7CompleteContent | Page 10

788 INVESTIGATIVE REPORT Involved and Uninvolved Psoriatic Keratinocytes Display a Resistance to Apoptosis that may Contribute to Epidermal Thickness Cecilia BIVIK EDING and Charlotta ENERBÄCK Ingrid Asp Psoriasis Research Center, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden Psoriasis is a common autoimmune skin disease. The aim of this study was to investigate whether the apop­ totic process is disturbed in psoriatic keratinocytes. In vitro culture of keratinocytes derived from both in- volved and uninvolved psoriatic skin, revealed higher viability and resistance to apoptosis following expo- sure to ultraviolet B, compared with cells from healthy controls. The position of apoptotic dysregulation was found to be upstream of cytochrome c release in the mitochondrial apoptotic pathway. Microarray trans- criptome analysis revealed that 87 genes were diffe- rentially expressed in both involved and uninvolved psoriatic keratinocytes compared with controls. Among these, a general upregulation of anti-apoptotic genes and downregulation of pro-apoptotic genes were iden- tified. This distinct apoptosis-resistant phenotype, un- related to the inflammatory component of the disease, implies that intrinsic abnormalities in keratinocytes may contribute to the pathogenesis of psoriasis. Key words: psoriasis; keratinocytes; apoptosis. Accepted Mar 22, 2017; Epub ahead of print Mar 28, 2017 Acta Derm Venereol 2017; 97: 788–796. Corr: Charlotta Enerbäck, Ingrid Asp Psoriasis Research Center, Depart- ment of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. E- mail: [email protected] P soriasis is a chronic inflammatory skin disease, af- fecting 2–3% of the population worldwide (1). Plaque psoriasis develops into red scaly patches, characterized by a dense inflammatory infiltrate, hyperproliferation of the epidermal keratinocytes, and increased angiogenesis. Overexpression of psoriasin (S100A7) contributes to dysregulated differentiation in psoriasis (2). The current general paradigm defines psoriasis as a T-cell-mediated disease targeting keratinocytes. However, there is evi- dence that identifies keratinocytes as important contri- butors to the pathogenesis of psoriasis. A number of studies report different keratinocyte pro- perties, not only in involved psoriatic skin, but also in normal-appearing uninvolved psoriatic skin that shows no signs of inflammation compared with normal skin. This suggests that an intrinsic abnormality in the kera- tinocytes contributes to the pathogenesis of the disease. Accelerated wound healing (3) and a disturbed calcium metabolism (4) have been demonstrated in uninvolved psoriatic skin compared with normal skin, as well as a doi: 10.2340/00015555-2656 Acta Derm Venereol 2017; 97: 788–796 hyper-responsiveness of uninvolved keratinocytes to growth-promoting T-cell lymphokines (5). A global gene expression profiling study demonstrated a “pre-psoriatic” gene expression signature in normal-appearing psoriatic skin (6), while another array study identified 562 genes that were differentially expressed in normal vs. unin- volved skin (7). Programmed cell death, or apoptosis, is an essential process to eliminate damaged, dysfunctional or exces- sive cells. I