Sensitization of IFN-gamma Jak-STAT signaling during macrophage activation. Academic Article uri icon

Overview

abstract

  • A general paradigm in signal transduction is ligand-induced feedback inhibition and the desensitization of signaling. We found that subthreshold concentrations of interferon-gamma (IFN-gamma), which did not activate macrophages, increased their sensitivity to subsequent IFN-gamma stimulation; this resulted in increased signal transducer and activator of transcription 1 (STAT1) activation and increased IFN-gamma#150;dependent gene activation. Sensitization of IFN-gamma signaling was mediated by the induction of STAT1 expression by low doses of IFN-gamma that did not effectively induce feedback inhibition. IFN-gamma signaling was sensitized in vivo after IFN-gamma injection, and STAT1 expression was increased after injection of lipopolysaccharide and in rheumatoid arthritis synovial cells. These results identify a mechanism that sensitizes macrophages to low concentrations of IFN-gamma and regulates IFN-gamma responses in acute and chronic inflammation.

publication date

  • August 12, 2002

Research

keywords

  • DNA-Binding Proteins
  • Interferon-gamma
  • Intracellular Signaling Peptides and Proteins
  • Macrophage Activation
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Signal Transduction
  • Trans-Activators

Identity

Scopus Document Identifier

  • 0036734498

Digital Object Identifier (DOI)

  • 10.1038/ni828

PubMed ID

  • 12172544

Additional Document Info

volume

  • 3

issue

  • 9