Abstract
While lipopolysaccharides (LPS) induce dendritic cell (DC) maturation and migration to lymph nodes, glucocorticoids such as dexamethazone (Dex) have a profound suppressive effect on immune response. The mechanisms that might control this suppressive effect of Dex have been extensively investigated in lymphocytes as possible targets. Much less is known on the effects of Dex on DC, although they are recognized to regulate immunity. To get insights into possible combined effects of Dex and LPS on DC functions, we have undertaken a genome-wide analysis of differentially expressed genes of DC treated with Dex alone, LPS alone, or both, using high-density oligonucleotide microarrays. Hierarchical clustering and principal component analysis (PCA) agreed in identifying 24 h as the time point that best discriminated the three treatments. Among the counteracting effects we have observed an inhibition of Dex on the LPS-induced up-regulation of the chemokine receptor CCR7. In vivo, Dex treatment blocked the LPS-induced migration of DC, which lost their ability to reach the draining lymph nodes. In addition, we observed a synergistic effect of Dex and LPS on the expression of the secreted lipocalin 24p3, which has been reported to induce apoptosis in T cells and thus may be related to immune suppression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute-Phase Proteins / biosynthesis
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Acute-Phase Proteins / genetics
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Acute-Phase Proteins / immunology
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology
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Cell Movement / drug effects*
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Cell Movement / immunology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Dexamethasone / pharmacology*
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Drug Interactions
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Gene Expression Profiling
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Glucocorticoids / pharmacology*
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Interleukins / biosynthesis
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Interleukins / genetics
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Interleukins / immunology
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Lipocalin-2
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Lipocalins
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Lipopolysaccharides / pharmacology*
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Mice
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NIH 3T3 Cells
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Oligonucleotide Array Sequence Analysis
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Oncogene Proteins / biosynthesis
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Oncogene Proteins / genetics
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Oncogene Proteins / immunology
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Principal Component Analysis
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Receptors, CCR7
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Receptors, Chemokine / biosynthesis
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Receptors, Chemokine / genetics
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Receptors, Chemokine / immunology
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T-Lymphocytes / immunology
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Transcription, Genetic / drug effects
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Transcription, Genetic / immunology
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Up-Regulation
Substances
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Acute-Phase Proteins
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Ccr7 protein, mouse
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Glucocorticoids
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Interleukins
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Lipocalin-2
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Lipocalins
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Lipopolysaccharides
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Oncogene Proteins
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RNA, Messenger
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Receptors, CCR7
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Receptors, Chemokine
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Lcn2 protein, mouse
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Dexamethasone