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

Nat Immunol. 2006 Apr;7(4):375-81. doi: 10.1038/ni1308. Epub 2006 Feb 19.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing / immunology*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Chemokine CXCL10
  • Chemokines, CXC / biosynthesis*
  • Chemokines, CXC / genetics
  • Chemokines, CXC / immunology
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology*
  • MAP Kinase Kinase 3 / immunology
  • MAP Kinase Kinase Kinases
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases / immunology
  • Myeloid Differentiation Factor 88
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Interferon / immunology
  • Receptors, Interferon / metabolism
  • Recombinant Proteins
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • p38 Mitogen-Activated Protein Kinases / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Chemokine CXCL10
  • Chemokines, CXC
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • Hnrpd protein, mouse
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • Receptors, Interferon
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • mitogen-activated protein kinase kinase kinase 11
  • MAP Kinase Kinase 3
  • Mitogen-Activated Protein Kinase Kinases