An IFN-gamma-inducible transcription factor, IFN consensus sequence binding protein (ICSBP), stimulates IL-12 p40 expression in macrophages. Academic Article uri icon

Overview

abstract

  • IL-12 is a cytokine that links innate and adaptive immunity. Its subunit p40 is induced in macrophages following IFN-gamma/LPS stimulation. Here we studied the role for IFN consensus sequence binding protein (ICSBP), an IFN-gamma/LPS-inducible transcription factor of the IFN regulatory factor (IRF) family in IL-12 p40 transcription. Macrophage-like cells established from ICSBP-/- mice did not induce IL-12 p40 transcripts, nor stimulated IL-12 p40 promoter activity after IFN-gamma/LPS stimulation, although induction of other inducible genes was normal in these cells. Transfection of ICSBP led to a marked induction of both human and mouse IL-12 p40 promoter activities in ICSBP+/+ and ICSBP-/- cells, even in the absence of IFN-gamma/LPS stimulation. Whereas IRF-1 alone was without effect, synergistic enhancement of promoter activity was observed following cotransfection of ICSBP and IRF-1. Deletion analysis of the human promoter indicated that the Ets site, known to be important for activation by IFN-gamma/LPS, also plays a role in the ICSBP activation of IL-12 p40. A DNA affinity binding assay revealed that endogenous ICSBP is recruited to the Ets site through protein-protein interaction. Last, transfection of ISCBP alone led to induction of the endogenous IL-12 p40 mRNA in the absence of IFN-gamma and LPS. Taken together, our results show that ICSBP induced by IFN-gamma/LPS, acts as a principal activator of IL-12p40 transcription in macrophages.

publication date

  • July 1, 2000

Research

keywords

  • Interferon-gamma
  • Interleukin-12
  • Macrophages
  • Repressor Proteins

Identity

Scopus Document Identifier

  • 0034235928

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.165.1.271

PubMed ID

  • 10861061

Additional Document Info

volume

  • 165

issue

  • 1