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-lymphocyt e infiltration associated with the disease. In this study the effect o f protein kinase C inhibitors on IL-8 production by human keratinocyte s in vitro was investigated. The anti-inflammatory and immunomodulator y compound auranofin -thio-beta-D-glucopyranose-2,3,4,6-tetraacetato-S ] [triethylphosphine] gold) is known to inhibit protein kinase C. In a ddition, auranofin has been shown to inhibit skin inflammation. As suc h, auranofin was also studied for its effect on IL-8 production. Auran ofin and staurosporine, inhibitors of protein kinase C, inhibited phor bol-myristate-acetate - stimulated IL-8 production. Northern analysis of IL-8 mRNA revealed that the inhibition of IL-8 production was assoc iated with an inhibition of IL-8 mRNA expression. In contrast, these c ompounds potentiated the minimal IL-8 protein and mRNA seen in respons e to interleukin-1 beta or tumor necrosis factor-alpha. These findings suggest that IL-8 synthesis may be either positively or negatively re gulated by protein kinase C depending on the stimulus.