IL-1? and IFN-? induce the regenerative epidermal phenotype of psoriasis in the transwell skin organ culture system. IFN-? up-regulates the expression of keratin 17 and keratinocyte transglutaminase via endogenous IL-1 production
✍ Scribed by Wei, Liu; Debets, Reno; Hegmans, Joost J; Benner, Robbert; Prens, Errol P.
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 542 KB
- Volume
- 187
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
Skin biopsies from healthy human skin and non-lesional skin from patients with psoriasis were cultured for 24 h and stimulated with interleukin-1 (IL-1 ) and interferon-(IFN-) in a skin organ culture model and the induction of the psoriasiform regenerative epidermal phenotype was analysed using immunostaining. In the presence of IL-1 , 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 1 from the basal to suprabasal keratinocytes, and induction of the expression of ICAM-1 and HLA-DR on basal keratinocytes. The effects of IL-1 in the organ cultures of normal skin could be completely neutralized by anti-IL-1 polyclonal antibodies. The effects of IFN-in healthy and non-lesional psoriatic skin were qualitatively similar to those of IL-1 . The IFN--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-is partially mediated via endogenous epidermal IL-1.