Suppression of Il-12 transcription in macrophages following Fc gamma receptor ligation. Academic Article uri icon

Overview

abstract

  • Ligating Fc gamma R on macrophages results in suppression of IL-12 production. We show that Fc gamma R ligation selectively down-regulates IL-12 p40 and p35 gene expression at the level of transcription. The region responsive to this inhibition maps to the Ets site of the p40 promoter. PU.1, IFN consensus sequence binding protein, and c-REL: form a complex on this element upon macrophage activation. Receptor ligation abolishes the binding of this PU.1-containing activation complex, and abrogates p40 transcription. A dominant-negative construct of PU.1 diminishes IL-12 p40 promoter activity and endogenous IL-12 p40 protein secretion. Thus, the specificity of IL-12 down-regulation following receptor ligation lies in the inhibition of binding of a PU.1-containing complex to the Ets site of the IL-12 promoter. These findings provide evidence demonstrating for the first time the importance of PU.1 in the transcriptional regulation of IL-12 gene expression.

publication date

  • April 1, 2001

Research

keywords

  • Down-Regulation
  • Interleukin-12
  • Macrophages
  • Receptors, IgG
  • Transcription Factors
  • Transcription, Genetic

Identity

Scopus Document Identifier

  • 0035313284

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.166.7.4498

PubMed ID

  • 11254706

Additional Document Info

volume

  • 166

issue

  • 7