Up-regulation of interleukin-1beta-stimulated interleukin-8 in human keratinocytes by nitric oxide.

Nitric oxide (NO) is able to regulate the expression of a number of inflammatory mediators. In this study, the effect of NO on the expression of the chemokine interleukin-8 (IL-8) by primary human keratinocytes and the lines KB and HaCaT was examined. Incubation with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) for 24 hr increased IL-8 protein only in HaCaT cells, partly due to the presence of constitutive interleukin-1 (IL-1). However, in combination with IL-1beta, SNAP enhanced both IL-8 mRNA and protein in all three cell types. Transfection of cells with an IL-8 promoter reporter gene construct showed that the effect of NO was at least partly due to transcriptional activation. Despite small variations in the response to NO by the three cell types, these results demonstrate that NO can up-regulate IL-1beta-stimulated IL-8 expression in human keratinocytes. This study provides a regulatory mechanism which may be important in the context of skin inflammation, and supports the role of NO as an inflammatory mediator in the skin.