Activation of peroxisome proliferator-activated receptor gamma leads to upregulation of ESE-3 expression in human monocyte-derived dendritic cells.
The transcription factor ESE-3 has been suggested to be involved in regulating the immunogenicity of human monocyte-derived dendritic cells (moDCs). While ESE-3 is not expressed in monocytes, it is upregulated during the differentiation of monocytes into dendritic cells (DCs) and highly expressed in immunogenic DCs while downregulated in tolerogenic DCs. Activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) during DC development has been shown to result in a rather tolerogenic cell population. In this study, we identified eight PPAR-γ binding sites upstream of the ESE-3 gene. Activation of the PPAR-γ pathway with synthetic PPAR-γ ligands during moDC generation resulted in upregulation of ESE-3b expression on mRNA and protein level, phenotypic alterations and reduced capacity of the cells to stimulate allogeneic T cells. This could be inhibited by blocking the PPAR-γ pathway with specific antagonists. Our results suggest PPAR-γ to be involved in the regulation of ESE-3b expression during moDC development and that ESE-3 expression is not correlated with the immunogenicity of DCs.
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
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Sprater
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Azeem
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Appel
D000813:Anilides / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000077288:Troglitazone; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D002839:Chromans; C403306:EHF protein, human; D008070:Lipopolysaccharides; D047495:PPAR gamma; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone