MOLECULAR MECHANISM OF INTERLEUKIN-8 GENE-EXPRESSION

A potent leukocyte chemotactic and activating cytokine, interleukin-8 (IL-8), is produced by numerous types of cells in response to inflammatory stimuli. Accumulating evidence indicate that the transcription of IL-8 gene requires the activation of either the combination of NF-kappa B and AP-1 or that of NF-kappa B and NF-IL6, depending on the type of cells. Alternatively, the activation of NF-kappa B is indispensable for IL-8 gene activation in any types of cells examined. On the other hand, an immunosuppressant, FK506, and a glucocorticoid inhibit the gene transcription as well as the production of IL-8. Molecular analyses of IL-8 gene repression by these agents revealed that both affected the activity of the transcription factor(s) bound to the NF-kappa B site, albeit in different ways, thereby suppressing IL-8 gene transcription. Collectively, IL-8 production seems to be controlled mainly at the activation step of the transcription factor(s) bound to the NF-kappa B site.