Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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CD40 Antigens / immunology
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Cells, Cultured
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Chemokine CCL19
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Chemokines, CC / genetics*
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Dendritic Cells / drug effects*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Glycoproteins / genetics*
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Humans
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Interferon-beta / immunology
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Interferon-beta / pharmacology*
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Interferon-gamma / immunology
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Interferon-gamma / pharmacology
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Interleukin-12 / genetics*
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Interleukin-12 Subunit p35
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Interleukin-12 Subunit p40
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins / genetics
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Minor Histocompatibility Antigens
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Multiple Sclerosis / drug therapy*
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Multiple Sclerosis / immunology
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Multiple Sclerosis / physiopathology
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Protein Biosynthesis
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Protein Subunits / genetics*
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Proteins / drug effects
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Receptors, Cytokine*
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Receptors, Immunologic / drug effects
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Receptors, Immunologic / genetics
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Th1 Cells / cytology
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Th1 Cells / immunology
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Th1 Cells / metabolism*
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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CCL19 protein, human
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CD40 Antigens
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Chemokine CCL19
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Chemokines, CC
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EBI3 protein, human
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Glycoproteins
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IL12A protein, human
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IL23A protein, human
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Interleukin-12 Subunit p35
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Interleukin-12 Subunit p40
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Interleukin-23
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Interleukin-23 Subunit p19
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Interleukins
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Minor Histocompatibility Antigens
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Protein Subunits
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Proteins
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RNA, Messenger
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Receptors, Cytokine
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Receptors, Immunologic
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p70 natural killer cell receptor
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Interleukin-12
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Interferon-beta
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Interferon-gamma