The Effects of Vitamin D on the Expression of IL-33 and Its Receptor ST2 in Skin Cells; Potential Implication for Psoriasis.

Justyna M Wierzbicka,Anna Olszewska,Bogusław Nedoszytko,Dorota Purzycka-Bohdan,Michał A Żmijewski,Aneta Szczerkowska-Dobosz,Joanna I Nowak,Roman J Nowicki,Anna Piotrowska

doi:10.3390/ijms222312907

Justyna M Wierzbicka, Anna Olszewska + Show 7 more

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https://doi.org/10.3390/ijms222312907

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Abstract

Interleukin 33 (IL-33) belongs to the IL-1 family and is produced constitutively by epithelial and endothelial cells of various organs, such as the skin. It takes part in the maintenance of tissue homeostasis, repair, and immune response, including activation of Th2 lymphocytes. Its involvement in pathogenesis of several inflammatory diseases including psoriasis was also suggested, but this is not fully understood. The aim of the study was to investigate expression of IL-33 and its receptor, ST2, in psoriasis, and the effects of the active form of vitamin D (1,25(OH)2D3) on their expression in skin cells. Here we examined mRNA and protein profiles of IL-33 and ST2 in 18 psoriatic patients and healthy volunteers by qPCR and immunostaining techniques. Potential effects of 1,25(OH)2D3 and its receptor (VDR) on the expression of IL-33 and ST2 were tested in cultured keratinocytes, melanocytes, fibroblasts, and basal cell carcinoma cells. It was shown that 1,25(OH)2D3 effectively stimulated expression of IL-33 and its receptor ST2’s mRNAs in a time-dependent manner, in keratinocytes and to the lesser extends in melanocytes, but not in fibroblasts. Furthermore, the effect of vitamin D on expression of IL-33 and ST2 was VDR-dependent. Finally, we demonstrated that the expression of mRNA for IL-33 was mainly elevated in the psoriatic skin but not in its margin. Interestingly, ST2 mRNA was downregulated in psoriatic lesion compared to both marginal tissue as well as healthy skin. Our data indicated that vitamin D can modulate IL-33 signaling, opening up new perspectives for our understanding of the mechanism of vitamin D action in psoriasis therapy.

Highlights

Beyond the effects on bone homeostasis, vitamin D exerts an impact on a variety of other organs or systems, including the skin and immune system
Given the recognized involvement of Interleukin 33 (IL-33) in psoriasis, the immunosuppressive activity of vitamin D and its therapeutic role in psoriasis, in the present study we investigated the effects of vitamin D on the expression of IL-33 and its receptor (ST2)
We investigated the effects of the major active form of vitamin D (1,25(OH)2 D3 ) on the expression of IL-33 at mRNA and protein levels (Figures 1 and 2) in skin-derived cell lines: keratinocytes, melanocytes, fibroblasts, and basal cell carcinoma cells. 1,25(OH)2 D3 effectively stimulated the expression of IL-33 and its receptor ST2 mRNAs in a time-dependent manner in keratinocytes and to a lesser extends in melanocytes (Figure 1A,B)

Summary

Introduction

Beyond the effects on bone homeostasis, vitamin D exerts an impact on a variety of other organs or systems, including the skin and immune system. Keratinocytes are a natural source of vitamin D, but due to the expression of the vitamin D receptor (VDR), they are target cells, which respond in an autocrine and paracrine manner [1]. Vitamin D exerts a number of actions in the skin, for example: it regulates cell proliferation, differentiation, apoptosis, and modulates immune activity [5,6]. Most of these actions are mediated by the vitamin D receptor (VDR), which, after 1,25(OH) D3 binding, interacts with the retinoid X receptor (RXR) and promotes the expression of the target genes [7]. Along with advances in molecular and clinical studies, vitamin D has gained attention as a potential player in the pathogenesis of various skin diseases, including psoriasis

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