IL-1β and IFN-γ induce the regenerative epidermal phenotype of psoriasis in the transwell skin organ culture system. IFN-γ up-regulates the expression of keratin 17 and keratinocyte transglutaminase via endogenous IL-1 production

Skin biopsies from healthy human skin and non‐lesional skin from patients with psoriasis were cultured for 24h and stimulated with interleukin‐1β(IL‐1β) and interferon‐γ (IFN‐γ) in a skin organ culture model and the induction of the psoriasiform regenerative epidermal phenotype was analysed using im...

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Bibliographic Details
Published in:The Journal of pathology 1999-02, Vol.187 (3), p.358-364
Main Authors: Wei, Liu, Debets, Reno, Hegmans, Joost J, Benner, Robbert, Prens, Errol P.
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Dermatology
Epidermis - metabolism
Female
Humans
Immunoenzyme Techniques
Interferon-gamma - pharmacology
interferon-γ
interleukin-1
Interleukin-1 - biosynthesis
Interleukin-1 - pharmacology
keratinocyte
Keratinocytes - enzymology
Keratins - metabolism
Male
Medical sciences
Middle Aged
organ culture
Organ Culture Techniques
psoriasis
Psoriasis - immunology
Psoriasis - metabolism
Psoriasis. Parapsoriasis. Lichen
Recombinant Proteins - pharmacology
Skin - immunology
Transglutaminases - metabolism
Up-Regulation
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Summary:Skin biopsies from healthy human skin and non‐lesional skin from patients with psoriasis were cultured for 24h and stimulated with interleukin‐1β(IL‐1β) and interferon‐γ (IFN‐γ) in a skin organ culture model and the induction of the psoriasiform regenerative epidermal phenotype was analysed using immunostaining. In the presence of IL‐1β, the psoriasiform regenerative epidermal phenotype was clearly induced. This involved strong up‐regulation of the expression of keratin 16, keratin 17, and keratinocyte transglutaminase (TGk) in the suprabasal layers, strong up‐regulation and a shift of the expression of keratin 5 and integrin β1from the basal to suprabasal keratinocytes, and induction of the expression of ICAM‐1 and HLA‐DR on basal keratinocytes. The effects of IL‐1β in the organ cultures of normal skin could be completely neutralized by anti‐IL‐1 polyclonal antibodies. The effects of IFN‐γ in healthy and non‐lesional psoriatic skin were qualitatively similar to those of IL‐1β. The IFN‐γ‐induced epidermal expression of keratin 17 and TGk could be completely blocked by culturing the biopsies in the presence of IL‐1ra or anti‐IL‐1 antibodies, while the induction of HLA‐DR and ICAM‐1 was not inhibited. The induction of the psoriasiform regenerative epidermal phenotype by IFN‐γ is partially mediated via endogenous epidermal IL‐1. Copyright © 1999 John Wiley & Sons, Ltd.
ISSN:0022-3417
1096-9896
DOI:10.1002/(SICI)1096-9896(199902)187:3<358::AID-PATH253>3.0.CO;2-8