Nature Immunology5, 1181 - 1189 (2004)
Published online: 3 October 2004; | doi:10.1038/ni1126
Amplification of IFN--induced STAT1 activation and inflammatory function by Syk and ITAM-containing adaptors
Ioannis Tassiulas1, 2, Xiaoyu Hu1, 3, Hao Ho1, Yogita Kashyap1, Paul Paik1, Yongmei Hu4, Clifford A Lowell4
& Lionel B Ivashkiv1, 2, 3
1
Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York 10021, USA.
2
Department of Medicine, Hospital for Special Surgery, New York, New York 10021, USA.
3
Graduate Program in Immunology, Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA.
4
Department of Laboratory Medicine, University of California, San Francisco, California 94143, USA.
Correspondence should be addressed to Lionel B Ivashkiv ivashkivl@hss.edu
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- (IFN-)−induced activation of the transcriptional activator STAT1 and inflammatory STAT1 target genes was enhanced in IFN--primed macrophages. Enhanced IFN- 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--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-.
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