IWR-1 attenuates the promotional effect of IL-36[gamma] in a mouse model of psoriasis

• Published in: BMC Immunology 2024, Vol.25 (1)
• Main Authors: Wang, Wen-Ming, Gao, Yi-Meng, Zheng, Xiao-Feng, Jin, Hong-Zhong
• Format: Report
• Language: English
• Subjects: Development and progression; Enzyme inhibitors; Physiological aspects; Psoriasis; Testing
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/s12865-024-00669-1

Psoriasis is a chronic inflammatory skin disease. The Wnt/[beta]-catenin signaling pathway is essential for the regulation of adult stem cells, homeostasis, and tissue regeneration; however, the relationship between this pathway and interleukin (IL)-36[gamma] in the pathogenesis of psoriasis remains unclear. In this study, psoriasiform model mice were established using imiquimod (IMQ) induction. Hematoxylin and eosin (H&E) staining was used to evaluate pathological morphologies, while immunohistochemistry was used to verify the expression patterns of [beta]-catenin and the inflammatory factors IL-6, IL-17 A, and interferon (IFN)-[gamma]. IL-36[gamma] treatment increased psoriasis area and severity index scores, and enhanced proliferation of keratinocytes in IMQ-induced psoriatic mice. The effects of IL-36[gamma] on the severity of psoriasiform lesions and epidermal hyperplasia were partly inhibited by IWR-1, which is an inhibitor of the Wnt/[beta]-catenin signaling pathway. Furthermore, the levels of proinflammatory cytokines and molecules involved in the Wnt/[beta]-catenin signaling pathway in psoriatic mouse skin, including IL-6, IL-17 A, IFN-[gamma], [beta]-catenin, and Dickkopf-1 (DKK1), were upregulated by treatment with IL-36[gamma]. Consistently, the effects of IL-36[gamma] on the inflammatory response and the Wnt/[beta]-catenin signaling pathway were alleviated by IWR-1. Taken together, our findings suggested that inhibition of the Wnt/[beta]-catenin signaling pathway may be useful in the alleviation of IL-36[gamma]-induced psoriasis-like lesions.