Regulation of interleukin-8 gene expression

J Interferon Cytokine Res. 1999 May;19(5):429-38. doi: 10.1089/107999099313866.


Interleukin-8 (IL-8), a member of the CXC chemokine family, is an important activator and chemoattractant for neutrophils and has been implicated in a variety of inflammatory diseases. IL-8 is secreted in a stimulus-specific manner by a wide variety of cell types and is regulated primarily at the level of gene transcription. Functional studies indicate that IL-8 transcriptional responses to proinflammatory mediators are rapid and require only 100 nucleotides of 5'-flanking DNA upstream of the TATA box. Within the IL-8 promoter sequence are DNA binding sites for the inducible transcription factors AP-1, NF-IL-6, and NF-kappaB. Transcription factors in these families bind the IL-8 promoter as dimers, and several distinct subunit combinations have been identified as important for IL-8 transcription. In addition, these factors can act in concert to synergistically activate the IL-8 promoter. AP-1 and NF-IL-6 physically interact with NF-kappaB, and functional cooperativity among the factors appears to be critical for optimal IL-8 promoter activity in different cell types. IL-8 transcription appears to be activated by a promoter recruitment mechanism where inducible transcription factor binding to the IL-8 promoter is required for binding of constitutively active TATA box-binding proteins and formation of a stable preinitiation complex. This review discusses the regulatory role these higher-order synergistic interactions play in IL-8 transcription and in generation of the stimulus-specific and cell type-specific patterns of IL-8 expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Gene Expression Regulation / physiology*
  • Humans
  • Interleukin-8 / genetics*
  • Molecular Sequence Data
  • NF-kappa B / physiology
  • Promoter Regions, Genetic
  • Transcription Factors / metabolism


  • Interleukin-8
  • NF-kappa B
  • Transcription Factors