MyD88-mediated stabilization of interferon-gamma-induced cytokine and chemokine mRNA.
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.
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Dongxu
D
Sun
Aihao
A
Ding
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D048371:MAP Kinase Kinase 3 / Q000276:immunology; D020930:MAP Kinase Kinase Kinases; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017471:Receptors, Interferon / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D007371:Interferon-gamma; D048371:MAP Kinase Kinase 3; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C000630987:Hnrpd protein, mouse; C507780:Myd88 protein, mouse