Dataset Information

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

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.

SUBMITTER: Kelemen E

PROVIDER: S-EPMC8745281 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Kelemen Evelyn E Ádám Éva É Sági Stella Márta SM Göblös Anikó A Kemény Lajos L Bata-Csörgő Zsuzsanna Z Széll Márta M Danis Judit J

International journal of molecular sciences 20220104 1

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 m ...[more]

PMID: 35008970

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Project description:Inflammatory bowel diseases (IBD) and psoriasis are chronic inflammatory conditions belonging to the heterogeneous group of immune-mediated inflammatory diseases (IMIDs). A significant bidirectional link between these two entities has been observed, conditioning an increased risk of IBD in patients with psoriasis and vice-versa. Biological therapies used for IBD may lead to the occurrence of psoriasis as a "paradoxical reaction." The objective of this study is to analyze the current evidence on the association between psoriasis and IBD, particularly finding case reports of the appearance or aggravation of psoriasis under therapy with interleukin-12/23 (IL-12/23) and IL-23 inhibitors. We conducted comprehensive research to identify studies examining the association between psoriasis and IBD and to find case presentations that reported the appearance or aggravation of psoriasis under biologic therapy with IL-12/23 and IL-23 inhibitors up to March 2024. Clinical trials for IL-12/23 and IL-23 inhibitors in IBD were analyzed to find cases of paradoxical psoriasis as registered adverse events. The sources of evidence are PubMed and ClinicalTrials.gov. For each included case report, data on patient characteristics concerning their age, sex, and comorbidities were selected. Moreover, information regarding the indication for biologic therapy, time to onset of paradoxical psoriasis after starting treatment, clinical presentation, and management of the paradoxical psoriasis was extracted. We found 10 reported cases of ustekinumab-induced new-onset or worsening psoriasis and one reported case of paradoxical psoriasis induced by risankizumab in the literature. Four cases of paradoxical psoriasis have been also registered in clinical trials involving ustekinumab treatment in IBD. Psoriasis can constitute a rare paradoxical adverse event of ustekinumab treatment, but further studies are needed to better clarify the cytokine imbalance that leads to this phenomenon induced by inhibition of IL-12/23 and IL-23. Still, few real-world data exist to draw any conclusions, but risankizumab may positively treat psoriasis induced by ustekinumab.

Dataset Information

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

Publications

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

Similar Datasets

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