Abstract: 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-xB and AP-! or that of NF-xB and NF-1L6, depending on the type of cells. Alternatively, the activation of NF-xB 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-xB 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- B site. J. Leukoc. Biol. 56: 554-558
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