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Topical vitamin D3 analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions

Authors


  • Funding sources
    This study was supported in part by Health and Labour Sciences Research Grants for Research on Hepatitis from the Ministry of Health, Labour and Welfare of Japan.

  • Conflicts of interest
    None declared.

  • E.D. and S.I. contributed equally to this work.

Shinichi Imafuku.
E-mail: dermatologist@mac.com

Abstract

Summary Background  Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D3 (1α,25-dihydroxyvitamin D3) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive.

Objectives  To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions.

Methods  Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription–polymerase chain reaction analyses to measure the expression levels of various cytokines.

Results  Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A− samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1β and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A− samples. Expression of cathelicidin was elevated in VD3A+ samples.

Conclusions  Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1β and TNF-α, thereby ameliorating psoriatic plaques.

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