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* Lymphocyte Cell Biology Section, NIAMS, and
Pediatric and Reproductive Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA;
INSERM U255, Curie Institute, Paris, France;
Department of Gastroenterology, Erasme Hospital, Brussels, Belgium; and
Department of Pediatrics, University of Leipzig, 04103 Leipzig, and
Department of Endocrinology, University of Düsseldorf, 40225 Düsseldorf, Germany
2Correspondence: Laboratoire d’Immunlogie Cellulaire et Clinique, Unité INSERM U255, Centre de Recherches Biomédicales des Cordeliers, 15 Rue de l’Ecole de Médecine, 75270 Paris Cedex 06 France. E-mail: jerome.galon{at}u255.bhdc.jussieu.fr
Glucocorticoids continue to be the major immunomodulatory agents used in clinical medicine today. However, their actions as anti-inflammatory and immunosuppressive drugs are both beneficial and deleterious. We analyzed the effect of glucocorticoids on the gene expression profile of peripheral blood mononuclear cells from healthy donors. DNA microarray analysis combined with quantitative TaqMan PCR and flow cytometry revealed that glucocorticoids induced the expression of chemokine, cytokine, and complement family members as well as of newly discovered innate immune-related genes, including scavenger and Toll-like receptors. In contrast, glucocorticoids repressed the expression of adaptive immune-related genes. Simultaneous inhibitory and stimulatory effects of glucocorticoids were found on inflammatory T helper subsets and apoptosis-related gene clusters. In cells activated by T cell receptor cross-linking, glucocorticoids down-regulated the expression of specific genes that were previously up-regulated in resting cells, suggesting a potential new mechanism by which they exert positive and negative effects. Considering the broad and continuously renewed interest in glucocorticoid therapy, the profiles we describe here will be useful in designing more specific and efficient treatment strategies.—Galon, J., Franchimont, D., Hiroi, N., Frey, G., Boettner, A., Ehrhart-Bornstein, M., O’Shea, J. J., Chrousos, G. P., Bornstein, S. R. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells.
Key Words: DNA microarray • clinical medicine • immune system
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
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