Regulatory effects of antipsoriatic agents on interleukin-1 alpha production by human keratinocytes stimulated with gamma interferon in vitro.
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)
Maruyama
K
K
Department of Dermatology, Fukushima Medical College, Japan.
Zhang
J Z
JZ
Nihei
Y
Y
Ono
I
I
Kaneko
F
F
D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016572:Cyclosporine; D002117:Calcitriol; D006854:Hydrocortisone