Nuclear factor-kappa B is essential for up-regulation of interleukin-8 expression in human amnion and cervical epithelial cells

Interleukin-8 (IL-8) is a cytokine which recruits and activates neutrophils into tissue stroma. It is present in uterine tissues and its concentration increases in the third trimester and with labour. The promoter region of t he IL-8 gene contains binding sites for the transcription factors, nuclear factor-kappa B (NF-kappaB), activator protein-1 (AP-1) and CCAAT/enhancer-b inding protein (C/EBP). These are in close proximity to each other and to t he coding region of the gene. This study used site-directed mutagenesis of each of these sites to examine the relative importance of each site in IL-8 gene expression in a cervical cell line and in amnion cells obtained befor e and after labour. We found that the NF-kappaB site was essential for basa l and IL-1 beta -stimulated gene expression in all cell types. Neither of t he other binding sites was consistently essential for gene expression but m ay have an additive role in promoter activity. We conclude that the NF-kapp aB binding site is essential for up-regulation of IL-8 gene expression in t hese uterine cell types. An increase in IL-8 expression has been shown to o ccur in the uterus in association with parturition and NF-kappaB binding to the promoter may be of importance at this time.