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Nat Immunol. 2006 Apr;7(4):375-81. Epub 2006 Feb 19.

MyD88-mediated stabilization of interferon-gamma-induced cytokine and chemokine mRNA.

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Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.


The MyD88 adaptor protein is critical in Toll-like receptor and interleukin 1 receptor (IL-1R) signaling, but has not been linked to interferon-gamma receptor (IFN-gammaR) signaling. Here we demonstrate that MyD88 increased the half-life but not the synthesis of IFN-gamma-induced mRNA transcripts encoding tumor necrosis factor and IFN-gamma-inducible protein 10. IFN-gamma stimulation triggered a physical association between the IFN-gammaR1 and MyD88. Transcript stabilization required activation of mixed-lineage kinase 3 and p38 mitogen-activated protein kinase and the presence of an adenine-uridine-rich element in the transcript's 3' untranslated region. These results demonstrate a MyD88-dependent post-transcriptional mechanism through which IFN-gamma can enhance the expression of genes encoding proinflammatory molecules.

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