Molecular mechanism of interleukin-8 gene expression

作者：Naofumi Mukaida, Shu‐ichi Okamoto, Yuji Ishikawa, Kouji Matsushima · 发表于：Journal of Leukocyte Biology · 年份：1994 · DOI：10.1002/jlb.56.5.554 · 被引用次数：454 · 研究领域：Cytokine Signaling Pathways and Interactions、NF-κB Signaling Pathways、Immune Response and Inflammation

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.