Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells.
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
Jerome
J
Lymphocyte Cell Biology Section, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA. jerome.galon@u255.bhdc.jussieu.fr
Franchimont
Denis
D
Hiroi
Naoki
N
Frey
Gregory
G
Boettner
Antje
A
Ehrhart-Bornstein
Monika
M
O'Shea
John J
JJ
Chrousos
George P
GP
Bornstein
Stefan R
SR
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000494:pharmacology*; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D005938:Glucocorticoids; D006680:HLA Antigens; D016023:Integrins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D003907:Dexamethasone; D003165:Complement System Proteins