Regulation of interleukin-8 gene expression by all-trans retinoic acid

Biochem Biophys Res Commun. 1995 May 25;210(3):898-906. doi: 10.1006/bbrc.1995.1742.


We have studied the relationship between interleukin-8 (IL-8) and interleukin-1 alpha (IL-1 alpha) release after stimulation with all-trans retinoic acid (ATRA) and tumor necrosis factor-alpha (TNF-alpha) in the human epithelial ovarian cancer cell line HOC-7. Both IL-1 alpha and IL-8 protein release were enhanced by treatment with ATRA and TNF-alpha after 48 h exposure. Blocking of IL-1 alpha activity in HOC-7 cells with either IL-1 receptor antagonist (IL-1ra) or a neutralizing antibody directed against IL-1 alpha resulted in a dose-dependent decrease of IL-8 release by ATRA, TNF-alpha and IL-1 alpha treated HOC-7 cells. Expression of IL-8 mRNA was enhanced by the individual stimuli, whereas co-treatment with IL-1ra resulted in a loss of IL-8 specific transcripts, except in TNF-alpha treated cells. Inhibition of de novo protein synthesis by cycloheximide (CHX) and simultaneous blocking of IL-1 alpha activity by IL-1ra for 24 h revealed that ATRA controls IL-8 gene expression transcriptionally and that the extent of IL-8 protein release can be markedly influenced by cellular expressed IL-1 alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Blotting, Northern
  • Cell Line
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-8 / biosynthesis*
  • Kinetics
  • Ovarian Neoplasms
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology
  • Transcription, Genetic / drug effects
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • Interleukin-1
  • Interleukin-8
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Tretinoin