Interferon-beta differentially regulates expression of the IL-12 family members p35, p40, p19 and EBI3 in activated human dendritic cells

J Neuroimmunol. 2002 Dec;133(1-2):60-71. doi: 10.1016/s0165-5728(02)00362-4.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD40 Antigens / immunology
  • Cells, Cultured
  • Chemokine CCL19
  • Chemokines, CC / genetics*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Glycoproteins / genetics*
  • Humans
  • Interferon-beta / immunology
  • Interferon-beta / pharmacology*
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Interleukin-12 / genetics*
  • Interleukin-12 Subunit p35
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / genetics
  • Minor Histocompatibility Antigens
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / physiopathology
  • Protein Biosynthesis
  • Protein Subunits / genetics*
  • Proteins / drug effects
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Cytokine*
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / genetics
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / immunology

Substances

  • CCL19 protein, human
  • CD40 Antigens
  • Chemokine CCL19
  • Chemokines, CC
  • EBI3 protein, human
  • Glycoproteins
  • IL12A protein, human
  • IL23A protein, human
  • Interleukin-12 Subunit p35
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Minor Histocompatibility Antigens
  • Protein Subunits
  • Proteins
  • RNA, Messenger
  • Receptors, Cytokine
  • Receptors, Immunologic
  • p70 natural killer cell receptor
  • Interleukin-12
  • Interferon-beta
  • Interferon-gamma