title: Activation of PAF-receptor induces regulatory dendritic cells through PGE2 and IL-10.
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.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-900, SP, Brazil.
authors.forename: Marianna M
authors.initials: MM
authors.lastname: Koga
authors.forename: Bruna
authors.initials: B
authors.lastname: Bizzarro
authors.forename: Anderson
authors.initials: A
authors.lastname: Sá-Nunes
authors.forename: Francisco J O
authors.initials: FJ
authors.lastname: Rios
authors.forename: Sonia
authors.initials: S
authors.lastname: Jancar
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000819:agonists / Q000235:genetics* / Q000276:immunology; D061251:Primary Cell Culture; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C515371:Ccr7 protein, mouse; D016861:Cyclooxygenase Inhibitors; D000949:Histocompatibility Antigens Class II; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D054400:Receptors, CCR7; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D016753:Interleukin-10; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Antigen-presentation; DC; IL-10; PAF; PGE(2)