Interferon-beta differentially regulates expression of the IL-12 family members p35, p40, p19 and EBI3 in activated human dendritic cells.
Interferon-beta is thought to provide clinical improvement to multiple sclerosis (MS) patients, in part, through its ability to suppress the generation of IL-12-dependent autoimmune T helper type 1 (Th1) cells by monocyte-derived dendritic cells (DC). We now describe how pre-incubation with 1000 U/ml of IFN-beta differentially regulates expression of multiple IL-12 family members in activated, immature human DC, inhibiting CD40/IFN-gamma-induced p35 and p40 message levels, while enhancing p19 and Epstein-Barr virus-induced gene 3 (EBI3) levels. IFN-beta-mediated inhibition of p40 mRNA and augmentation of p19 mRNA both require de novo protein synthesis. These findings indicate that IFN-beta will be found to have contrasting effects on DC secretion of the various IL-12 family homo- and heterodimers.
van Seventer
Jean Maguire
JM
Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA. jvsevent@bu.edu
Nagai
Taro
T
van Seventer
Gijs A
GA
D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000235:genetics*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D016899:Interferon-beta / Q000276:immunology / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000235:genetics*; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000235:genetics*; D011506:Proteins / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000187:drug effects / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
C515460:CCL19 protein, human; D019013:CD40 Antigens; D054415:Chemokine CCL19; D019742:Chemokines, CC; C097732:EBI3 protein, human; D006023:Glycoproteins; C508858:IL12A protein, human; C508840:IL23A protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits; D011506:Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; C098698:p70 natural killer cell receptor; D018664:Interleukin-12; D016899:Interferon-beta; D007371:Interferon-gamma