Peroxisome proliferator-activated receptor gamma activators inhibit interleukin-12 production in murine dendritic cells

FEBS Lett. 2000 Dec 15;486(3):261-6. doi: 10.1016/s0014-5793(00)02319-x.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily. They are divided into three subtypes (alpha, beta or delta, and gamma) and are involved in lipid and glucose homeostasis and in the control of inflammation. In this study, we analyzed the expression of PPARs in murine dendritic cells (DCs), the most potent antigen presenting cells. We find that immature as well as mature spleen-derived DCs express PPARgamma, but not PPARalpha, mRNA and protein. We also show that the PPARgamma activator rosiglitazone does not interfere with the maturation of DCs in vitro nor modifies their ability to activate naive T lymphocytes in vivo. Finally, we present evidence that PPARgamma activators down-modulate the CD40-induced secretion of interleukin-12, a potent Th1-driving factor. These data suggest a possible role for PPARgamma in the regulation of immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • CD40 Antigens / metabolism
  • CD40 Antigens / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dimethyl Sulfoxide / pharmacology
  • Interferon-gamma / metabolism
  • Interleukin-12 / biosynthesis*
  • Interleukins / metabolism
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • RNA, Messenger / biosynthesis
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Rosiglitazone
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / agonists
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Antigens, CD
  • CD40 Antigens
  • Interleukins
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone
  • Interleukin-12
  • Interferon-gamma
  • Prostaglandin D2
  • Dimethyl Sulfoxide