| Abstract: | 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. |
