Tassiulas Ioannis, Hu Xiaoyu, Ho Hao, Kashyap Yogita, Paik Paul, Hu Yongmei, Lowell Clifford A, Ivashkiv Lionel B
Arthritis and Tissue Degeneration Program, Department of Medicine, Hospital for Special Surgery, New York, New York 10021, USA.
Nat Immunol. 2004 Nov;5(11):1181-9. doi: 10.1038/ni1126. Epub 2004 Oct 3.
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.
