Differential response of the murine IL-12 p35 gene to lipopolysaccharide compared with interferon-gamma and CD40 ligation

Hema Vaidyanathan, John D. Gentry, Aaron Weatherman, Steven D. Schwartzbach, Thomas M Petro

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Expression of the heterodimeric cytokine interleukin-(IL-)12 is induced by pattern recognition receptors responding to microbial stimuli such as lipopolysaccharide (LPS) and products of the immune system such as interferon-gamma (IFN-γ) and CD40L. The formation of bioactive IL-12 requires equimolar synthesis of p35 and p40 subunits. However, p35 expression limits the amount of IL-12 formed. Transcription of the gene for the p35 subunit of IL-12 initiates within the first exon, an alternate first exon (exon 1a), or second exon. Here we show that LPS and IFN-γ/CD40 ligation increase the amount of total p35 mRNA in splenic adherent cells (SAC) to a similar extent. However, the exon 1 transcript was a smaller fraction of total p35 mRNA in IFN-γ/CD40-stimulated cells than in unstimulated or LPS-stimulated cells. Despite comparable levels of total p35 mRNA, LPS-induced p35 exon 1 transcripts led to significantly more bioactive IL-12 from SAC than IFN-γ/CD40-induced exon 1a/exon 2 transcripts as measured by ELISA. The data suggest that LPS-inducible p35 synthesis from exon 1 p35 transcripts leads to greater amount of bioactive IL-12 than IFN-γ/CD40-induced p35 expression from alternate p35 exon 1a/exon 2 transcripts.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCytokine
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 1 2001

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Keywords

  • CD40
  • IFN-γ
  • IL-12
  • Lipopolysaccharide
  • Macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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