Activation of PAF-receptor induces regulatory dendritic cells through PGE2 and IL-10

Prostaglandins Leukot Essent Fatty Acids. 2013 Oct;89(5):319-26. doi: 10.1016/j.plefa.2013.09.003. Epub 2013 Sep 26.

Abstract

Activation of the platelet-activating factor receptor (PAFR) in macrophages is associated with suppressor phenotype. Here, we investigated the PAFR in murine dendritic cells (DC). Bone marrow-derived dendritic cells (BALB/c) were cultured with GM-CSF and maturation was induced by LPS. The PAFR antagonists (WEB2086, WEB2170, PCA4248) and the prostaglandin (PG) synthesis inhibitors (indomethacin, nimesulide and NS-398) were added before LPS. Mature and immature DCs expressed PAFR. LPS increased MHCII, CD40, CD80, CD86, CCR7 and induced IL-10, IL-12, COX-2 and PGE2 expression. IL-10, COX-2 and PGE2 levels were reduced by PAFR antagonists and increased by cPAF. The IL-10 production was independent of PGs. Mature DCs induced antigen-specific lymphocyte proliferation. PAFR antagonists or PG-synthesis inhibitors significantly increased lymphocyte proliferation. It is proposed that PAF has a central role in regulatory DC differentiation through potentiation of IL-10 and PGE2 production.

Keywords: Antigen-presentation; DC; IL-10; PAF; PGE(2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / immunology
  • Cyclooxygenase Inhibitors / pharmacology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dinoprostone / metabolism*
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Membrane Glycoproteins / agonists
  • Platelet Membrane Glycoproteins / genetics*
  • Platelet Membrane Glycoproteins / immunology
  • Primary Cell Culture
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / immunology
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / immunology
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Antigens, CD
  • Ccr7 protein, mouse
  • Cyclooxygenase Inhibitors
  • Histocompatibility Antigens Class II
  • IL10 protein, mouse
  • Lipopolysaccharides
  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoproteins
  • Receptors, CCR7
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
  • Interleukin-10
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Dinoprostone