Interleukin-8 production is regulated by protein kinase C in human keratinocytes.
Interleukin-8 (IL-8) is a potent pro-inflammatory molecule present in high amounts in psoriatic skin. Here it may play an important role in the keratinocyte hyperproliferation and the neutrophil and T-lymphocyte infiltration associated with the disease. In this study the effect of protein kinase C inhibitors on IL-8 production by human keratinocytes in vitro was investigated. The anti-inflammatory and immunomodulatory compound auranofin ([1-thio-beta-D-glucopyranose-2,3,4,6-tetraacetato-S] [triethylphosphine] gold) is known to inhibit protein kinase C. In addition, auranofin has been shown to inhibit skin inflammation. As such, auranofin was also studied for its effect on IL-8 production. Auranofin and staurosporine, inhibitors of protein kinase C, inhibited phorbol-myristate-acetate-stimulated IL-8 production. Northern analysis of IL-8 mRNA revealed that the inhibition of IL-8 production was associated with an inhibition of IL-8 mRNA expression. In contrast, these compounds potentiated the minimal IL-8 protein and mRNA seen in response to interleukin-1 beta or tumor necrosis factor-alpha. These findings suggest that IL-8 synthesis may be either positively or negatively regulated by protein kinase C depending on the stimulus.
Chabot-Fletcher
M
M
Department of Inflammation Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
Breton
J
J
Lee
J
J
Young
P
P
Griswold
D E
DE
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D001310:Auranofin / Q000494:pharmacology; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D016209:Interleukin-8; D001310:Auranofin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate