Multiple control of interleukin-8 gene expression

J Leukoc Biol. 2002 Nov;72(5):847-55.


Interleukin (IL)-8, a prototypic human chemokine, was detected more than a decade ago as the founding member of the chemokine superfamily. One of the most remarkable properties of IL-8 is the variation of its expression levels. In healthy tissues, IL-8 is barely detectable, but it is rapidly induced by ten- to 100-fold in response to proinflammatory cytokines such as tumor necrosis factor or IL-1, bacterial or viral products, and cellular stress. Recently, significant advances in the understanding of signaling pathways, which coordinately regulate IL-8 transcription as well as mRNA stabilization in response to external stimuli, have been made. Maximal IL-8 amounts are generated by a combination of three different mechanisms: first, derepression of the gene promoter; second, transcriptional activation of the gene by nuclear factor-kappaB and JUN-N-terminal protein kinase pathways; and third, stabilization of the mRNA by the p38 mitogen-activated protein kinase pathway. In that way, cells are able to rapidly increase and at the same time, to fine-tune the amount of IL-8 secreted and thereby control the extent of leukocytes attracted to sites of tissue injury.

Publication types

  • Review

MeSH terms

  • Animals
  • Base Sequence
  • DNA-Binding Proteins*
  • Gene Expression Regulation
  • Humans
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics*
  • MAP Kinase Kinase Kinases / physiology
  • Mice
  • Mitogen-Activated Protein Kinases / physiology
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • RNA Stability
  • Repressor Proteins / physiology
  • Signal Transduction
  • Transcription Factors / physiology
  • Transcription, Genetic
  • Transcriptional Activation


  • DNA-Binding Proteins
  • Interleukin-8
  • NF-kappa B
  • NKRF protein, human
  • Repressor Proteins
  • Transcription Factors
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases