Psoriasis-Associated Inflammatory Conditions Induce IL-23 mRNA Expression in Normal Human Epidermal Keratinocytes.

Evelyn Kelemen,Stella Márta Sági,Anikó Göblös,Judit Danis,Lajos Kemény,Éva Ádám,Zsuzsanna Bata-Csörgő,Márta Széll

doi:10.3390/ijms23010540

Abstract

Psoriasis is a multifactorial, chronic inflammatory skin disease, the development of which is affected by both genetic and environmental factors. Cytosolic nucleic acid fragments, recognized as pathogen- and danger-associated molecular patterns, are highly abundant in psoriatic skin. It is known that psoriatic skin exhibits increased levels of IL-23 compared to healthy skin. However, the relationship between free nucleic acid levels and IL-23 expression has not been clarified yet. To examine a molecular mechanism by which nucleic acids potentially modulate IL-23 levels, an in vitro system was developed to investigate the IL-23 mRNA expression of normal human epidermal keratinocytes under psoriasis-like circumstances. This system was established using synthetic nucleic acid analogues (poly(dA:dT) and poly(I:C)). Signaling pathways, receptor involvement and the effect of PRINS, a long non-coding RNA previously identified and characterized by our research group, were analyzed to better understand the regulation of IL-23 in keratinocytes. Our results indicate that free nucleic acids regulate epithelial IL-23 mRNA expression through the TLR3 receptor and specific signaling pathways, thereby, contributing to the development of an inflammatory milieu favorable for the appearance of psoriatic symptoms. A moderate negative correlation was confirmed between the nucleic-acid-induced IL-23 mRNA level and the rate of its decrease upon PRINS overexpression.

Highlights

IntroductionChronic inflammatory skin disease affecting 2% of the population and has been known since ancient times
Publisher’s Note: MDPI stays neutralPsoriasis is a multifactorial, chronic inflammatory skin disease affecting 2% of the population and has been known since ancient times
To identify genes responding with altered expression in normal human epidermal keratinocytes (NHEKs) to treatment with the synthetic nucleic acid analogues poly(I:C) and poly(dA:dT), a qPCR array containing

Summary

Introduction

Chronic inflammatory skin disease affecting 2% of the population and has been known since ancient times. Both congenital predisposition and environmental factors play a role in its development. Well-demarcated, erythematous oval plaques with silvery scales are the prominent signs of the most common form, the plaque-type psoriasis. This symptom is caused by the abnormal proliferation and differentiation of basal keratinocytes and their dysregulated interplay with professional immune cells. Plaques are surrounded by clinically healthy-looking skin, which is referred to as non-lesional or uninvolved skin. Despite the fact that the uninvolved skin of psoriasis patients appears macroscopically identical to normal skin, it contains molecular, cellular and extracellular alterations and, in several aspects, has a pre-psoriatic phenotype [3–7]

Objectives

Methods

Results

Conclusion