Effect of gamma-interferon on IL-1 alpha, beta and receptor antagonist production by normal human keratinocytes.
In inflammatory dermatoses, activated T cells produce interferon-gamma (IFN-gamma), which interacts with keratinocytes and contributes to the direct activation of these cells by inducing, among other factors, the expression of HLA-DR antigens and intercellular adhesion molecule-1. However, the action of IFN-gamma on epidermal cell cytokine production is not known. Our aim was to assess the effect of IFN-gamma on the production of IL-1 by normal human keratinocytes cultured in low calcium medium (MCDB153). In comparison with controls, the addition of non-toxic IFN-gamma concentrations (50-500 U/ml) to cell cultures induced a significant increase of IL-1 alpha and IL-1 beta production predominantly after 100 U/ml treatment in the cell extracts as well as in the supernatants at 24h and 48h. The production of the antagonist, IL-1RA, was also enhanced and the effect of the critical concentration (100 U/ml) was more evident. However, the absence of a characteristic dose response could not be explained by an antiproliferative effect of high IFN-gamma concentrations (250 and 500 U/ml) on cultured keratinocytes or by the induction of the nuclear stress protein, Hsp72, two phenomena known to down-regulate IL-1 biosynthesis. In conclusion, the modifications in keratinocyte IL-1 production under IFN-gamma stimulation can contribute to activate the epidermal cells and thus involve them in the local immune response.
INSERM U 346 Clinique Dermatologique, Hôpital Ed.-Herriot, Lyon, France.
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A
Guéniche
J
J
Viac
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M
Charveron
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D
Schmitt
D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007700:Kinetics; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000096:biosynthesis*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D007371:Interferon-gamma