Role of interleukin-36γ induced by ultraviolet radiation in chronic actinic dermatitis

• Published in: Photodermatology, photoimmunology & photomedicine Vol. 39; no. 6; pp. 598 - 606
• Main Authors: Wang, Li, Tu, Yunhua, Wu, Wenjuan, Tu, Ying, Yang, Zhenghui, Chai, Yanjie, Yang, Xinwang, He, Li
• Format: Journal Article
• Language: English
• Published: England 01.11.2023
• Subjects: chronic actinic dermatitis; eosinophils; IL-36γ; IgE; ultraviolet
• ISSN: 0905-4383; 1600-0781
• DOI: 10.1111/phpp.12903

Chronic actinic dermatitis (CAD) is an immune-mediated photodermatosis characterized by a high eosinophil count and total immunoglobulin E (IgE) in the peripheral blood of patients. At present, however, the reasons for their elevation remain unclear. The current study aimed to detect changes in inflammatory cytokines in CAD and explore their role in this disease. Enzyme-linked immunosorbent assay and Luminex assay were conducted to measure inflammatory factor levels. Immunohistochemical analysis and quantitative real-time polymerase chain reaction were performed to evaluate the expression levels of interleukin-36γ (IL-36γ), IL-8, chemokine (C-C motif) ligand 17 (CCL17), and CCL18. CCK8 kits were used to assess cell proliferation. Immunofluorescence was used to detect nuclear factor κB (NF-κB) p65 nuclear translocation. Western blot analysis was performed to detect the protein expression level of phosphorylated NF-κB (p-NF-κB) p65. Hematoxylin and eosin and Masson trichrome staining were applied to observe histological changes in a chronic photo-damaged mouse model. Eosinophils, total IgE, IL-36γ, IL-8, tumor necrosis factor α, CCL17, and CCL18 were elevated in CAD. Of note, IL-36γ promoted the proliferation of eosinophilic cells (EOL-1) and the production of IgE in peripheral blood mononuclear cells. IL-36γ also promoted the production of IL-8 and CCL18 in immortalized human keratinocytes (HaCaT cells), while ultraviolet radiation (UVR)-induced IL-36γ via activation of the NF-κB signaling pathway. IL-36γ was involved in the pathogenesis of CAD and UVR contributed to the production of IL-36γ, which may provide a novel therapeutic target for CAD.