IL-1 beta and IFN-gamma induce the regenerative epidermal phenotype of psoriasis in the transwell skin organ culture system. IFN-gamma 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 24 h and stimulated with interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) 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 beta, 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 beta 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 beta in the organ cultures of normal skin could be completely neutralized by anti-IL-1 polyclonal antibodies. The effects of IFN-gamma in healthy and non-lesional psoriatic skin were qualitatively similar to those of IL-1 beta. The IFN-gamma-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-gamma is partially mediated via endogenous epidermal IL-1.
Department of Dermatology, General Hospital of the Air Force, Beijing, P.R. China.
L
L
Wei
R
R
Debets
J J
JJ
Hegmans
R
R
Benner
E P
EP
Prens
D000328:Adult; D000368:Aged; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology*; D015603:Keratinocytes / Q000201:enzymology; D007633:Keratins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000276:immunology; D011503:Transglutaminases / Q000378:metabolism*; D015854:Up-Regulation
D007375:Interleukin-1; D011994:Recombinant Proteins; D007633:Keratins; D007371:Interferon-gamma; D011503:Transglutaminases