Amplification of IFN-alpha-induced STAT1 activation and inflammatory function by Syk and ITAM-containing adaptors. Academic Article uri icon

Overview

abstract

  • A key function of interferons is priming multiple cell types for enhanced activation by cytokines and inflammatory factors, including tumor necrosis factor, bacterial lipopolysaccharide and interferons themselves. Here we show that interferon-alpha (IFN-alpha)-induced activation of the transcriptional activator STAT1 and inflammatory STAT1 target genes was enhanced in IFN-gamma-primed macrophages. Enhanced IFN-alpha signaling and proinflammatory function were dependent on the tyrosine kinase Syk and on adaptor proteins that activate Syk through immunoreceptor tyrosine activation motifs. Increased STAT1 expression contributed to enhanced IFN-alpha-induced STAT1 activation in primed macrophages. These results identify a mechanism by which crosstalk between cytokine and immune cell-specific immunoreceptor tyrosine activation motif-dependent signaling pathways regulates macrophage responses to IFN-alpha.

publication date

  • October 3, 2004

Research

keywords

  • Adaptor Proteins, Vesicular Transport
  • DNA-Binding Proteins
  • Enzyme Precursors
  • Interferon-alpha
  • Protein-Tyrosine Kinases
  • Trans-Activators

Identity

Scopus Document Identifier

  • 9244249240

Digital Object Identifier (DOI)

  • 10.1038/ni1126

PubMed ID

  • 15467722

Additional Document Info

volume

  • 5

issue

  • 11