Regulatory Effects of Antipsoriatic Agents on Interleukin-1 α Production by Human Keratinocytes Stimulated with Gamma Interferon in vitro

Abstract

It is known that keratinocytes produce and secrete interleukin-1 (IL-1) de novo and that this process can be enhanced by various stimulators. IL-1 has been shown to be a potent proinflammatory cytokine which mediates inflammation in various cutaneous disorders. It has also been demonstrated that gamma-interferon (IFN-gamma) which is released from infiltrated T cells can be detected in inflamed lesional sites. In order to understand the effects of IFN-gamma on IL-1 production by keratinocytes in such inflammatory lesions, normal human keratinocytes (NHKs) and human squamous cell carcinoma cell line (HSC-1) cells were cultivated with recombinant human IFN-gamma (rIFN-gamma) and IL-1 levels were measured by ELISA. The effects of antipsoriatic agents such as hydrocortisone (HC), cyclosporin A (CsA), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its analogue MC903 on IL-1 production by keratinocytes were also investigated. IL-1 release by both NHK and HSC-1 cells was accelerated by stimulation with rIFN-gamma dose-dependently, although IL-1 alpha was released only transiently by rIFN-gamma-stimulated NHKs in serum-free keratinocyte growth medium containing HC. Antihuman IFN-gamma antibody inhibited IL-1 alpha release by HSC-1 cells stimulated with rIFN-gamma, suggesting that IL-1 alpha release from keratinocytes is upregulated by IFN-gamma. HC (5 micrograms/ml), 1,25(OH)2D3 (10(-6) M) and MC903 (10(-6) M), but not CsA (5 micrograms/ml), inhibited IL-1 alpha production by HSC-1 cells stimulated with 100 U/ml of rIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)