Response of keratinocytes from normal and psoriatic epidermis to interferon‐γ differs in the expression of zinc‐α2‐glycoprotein and cathepsin D

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Abstract
Psoriasis is a T cell-mediated inflammatory disease characterized by hyperproliferation and by aberrant differentiation. We found cathepsin D and zinc-α2-glycoprotein, two catalytic enzymes associated with apoptosis and desquamation, to be present in the stratum corneum of the normal epidermis but absent from the psoriatic plaque. Psoriasis is characterized by an altered response to interferon-γ (IFN-γ), including the induction of apoptosis in normal but not in psoriatic keratinocytes, often with opposite effects on gene expression of suprabasal proteins. We found that IFN-γ binding and signaling were attenuated in psoriasis: The IFN-γ receptor, the signal transducer and activator of transcription STAT-1, and the interferon regulatory factor IRF-1 were strongly up-regulated by IFN-γ in normal keratinocytes, but not in psoriatic ones. IFN-γ strongly up-regulated the expression of the catalytic enzymes cathepsin D and zinc-α2-glyco-protein in normal keratinocytes but down-regulated them in psoriatic ones; the reverse was true of the apoptotic suppressor bcl-2. We believe that the aberrant response to IFN-γ plays a central role in the pathophysiology of psoriasis, particularly the disruption of apoptosis and desquamation.—Chen, S.-H., Arany, I., Apisarnthanarax, N., Rajaraman, S., Tyring, S. K., Horikoshi, T., Brysk, H., Brysk, M. M. Response of keratinocytes from normal and psoriatic epidermis to interferon-γ differs in the expression of zinc-α2-glycoprotein and cathepsin D. FASEB J. 14, 565–571 (2000)
Funding Information
  • Shiga University of Medical Science