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

• Published in: International journal of molecular sciences 2022-01, Vol.23 (1), p.540
• Main Authors: Kelemen, Evelyn, Ádám, Éva, Sági, Stella Márta, Göblös, Anikó, Kemény, Lajos, Bata-Csörgő, Zsuzsanna, Széll, Márta, Danis, Judit
• Format: Article
• Language: English
• Subjects: Acids; Antigens; Binding sites; Cells, Cultured; Chemokines; Cytokines; Dendritic cells; Disease Susceptibility; Epidermal Cells; Gene Expression; Gene Expression Regulation; Humans; Interleukin 23; Interleukin-23 - genetics; Keratinocytes; Keratinocytes - metabolism; Keratinocytes - pathology; Nucleic acids; Pathogenesis; Peptides; Poly I-C - pharmacology; Polyinosinic:polycytidylic acid; Psoriasis; Psoriasis - etiology; Psoriasis - metabolism; Psoriasis - pathology; RNA, Messenger - genetics; Signal Transduction; Signs and symptoms; Skin; Skin diseases; TLR3 protein; Toll-Like Receptor 3 - metabolism; Toll-like receptors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23010540

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.