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

Irene Seegmüller1, Hans Häcker, Hermann Wagner

  • 1Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Germany.

European Journal of Immunology
|March 21, 2003
PubMed

Insights

Interleukin-4 (IL-4) inhibits interleukin-12 (IL-12) p40 production in macrophages stimulated by bacterial CpG-DNA. This regulation occurs through reduced mRNA stability and affected promoter activity, impacting Th1/Th2 immune responses.

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Interleukin-12 (IL-12) and Interleukin-4 (IL-4) are key cytokines in T helper cell polarization.
  • IL-4 is known to inhibit IL-12 p40 production in dendritic cells.
  • Macrophages also play a role in immune responses involving IL-12.

Purpose of the Study:

  • To investigate the effect of IL-4 on IL-12 p40 production in macrophages stimulated with bacterial CpG-DNA.
  • To elucidate the molecular mechanisms by which IL-4 regulates IL-12 p40 expression in macrophages.

Main Methods:

  • Stimulation of macrophages with bacterial CpG-DNA.
  • Treatment with IL-4.
  • Analysis of IL-12 p40 mRNA stability.
  • Assessment of IL-12 p40 promoter activity.
  • Evaluation of early signal transduction pathways.

Main Results:

  • Macrophages produce IL-12 p40 in response to CpG-DNA in an IL-4-sensitive manner.
  • IL-4 reduces IL-12 p40 production by decreasing IL-12 p40 mRNA stability.
  • IL-4 also affects the promoter activity of the IL-12 p40 gene.
  • IL-4 does not impact early CpG-DNA-induced signal transduction.
  • IL-4 accelerates IL-12 p40 mRNA degradation when de novo transcription is blocked.

Conclusions:

  • IL-4 regulates IL-12 p40 expression in macrophages through modulation of both promoter activity and mRNA stability.
  • These findings provide insights into the intricate regulation of immune responses involving IL-12 and IL-4 signaling.

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