Production and gene expression of IL8

Various stimuli, including LPS, proinflammatory cytokines and viruses, induce IL-8 mRNA very rapidly in a variety of cells, including PBMCs, fibroblasts, endothelial cells and keratinocytes. The activation of gene transcription as well as stabilization of its mRNA are responsible for the accumulation of IL-8 mRNA.

IL-8 genomic DNA consists of four exons and three introns. The transcription of IL-8 gene requires, in a cell type-specific manner, the activation of three cis elements in the 5'-flanking region of the IL-8 gene: AP-1 (-126 to -120 bp), NF-IL6 (-94 to -81 bp), and NFkB binding sites (-80 to -70 bp). NFkB is the most crucial transcription factor and activates IL-8 gene transcription in cooperation with NF-IL6 or AP-1. In addition, several agents such as glucocorticoids, interferon a/(3, and FK506, inhibit IL-8 gene transcription by interfering with the activation of NFkB.

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