IL-4 regulates IL-12 p40 expression post-transcriptionally as well as via a promoter-based mechanism

Eur J Immunol. 2003 Feb;33(2):428-33. doi: 10.1002/immu.200310017.

Abstract

IL-12 and IL-4, respectively, dominate Th1 versus Th2 polarization. Additionally IL-4 can inhibit IL-12 p40 production in DC. Here we show that macrophages respond to bacterial CpG-DNA with IL-12 p40 production in an IL-4-sensitive manner. Analysis of the molecular mechanism of this inhibition shows that IL-4 acts by reducing the stability of IL-12 p40 mRNA as well as by affecting promoter activity. IL-4 did not affect early CpG-DNA-induced signal transduction. However, IL-4 reduced the activity of the IL-12 p40 promoter and when de novo transcription of IL-12 p40 mRNA was blocked, IL-4 led to acceleration of IL-12 p40 mRNA degradation. These data show that IL-4 regulates IL-12 p40 expression by influencing promoter activity and by interfering with mRNA stability.

MeSH terms

  • Animals
  • Cell Line / drug effects
  • CpG Islands
  • Dactinomycin / pharmacology
  • Genes, Reporter
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / genetics
  • Interleukin-12 Subunit p40
  • Interleukin-4 / pharmacology*
  • Luciferases / biosynthesis
  • Macrophages / metabolism
  • Mice
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Promoter Regions, Genetic / drug effects*
  • Protein Subunits / biosynthesis*
  • Protein Subunits / genetics
  • RNA Processing, Post-Transcriptional / drug effects*
  • RNA, Messenger / metabolism*
  • Recombinant Fusion Proteins / biosynthesis
  • Transfection

Substances

  • Interleukin-12 Subunit p40
  • Nucleic Acid Synthesis Inhibitors
  • Protein Subunits
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Interleukin-12
  • Dactinomycin
  • Interleukin-4
  • Luciferases