title: Dexamethasone modulates interleukin-12 production by inducing monocyte chemoattractant protein-1 in human dendritic cells.
abstract: Glucocorticoids have long been used as first-line immunosuppressants, although their precise mechanism of action has not been fully elucidated yet. This study evaluated the gene and protein expression of monocyte chemoattractant protein-1 (MCP-1), and its relationship with interleukin-12 and interleukin-10 synthesis, in human monocyte-derived dendritic cells exposed to dexamethasone. Dendritic cells were differentiated in the presence or in the absence of dexamethasone and then activated by IFN-gamma+soluble CD40 ligand; the gene and protein expression of target cytokines was measured by real-time PCR and ELISA, respectively. Our results showed that dexamethasone-primed mature dendritic cells expressed low levels of interleukin-12, and, at the opposite, high levels of interleukin-10 and MCP-1. Transfection experiments confirmed the ability of dexamethasone to activate MCP-1 gene promoter. Dexamethasone increased also MCP-2, but not MCP-3 synthesis, and the gene expression of CC chemokine receptor-2 by mature dendritic cells. The addition of anti-MCP-1 blocking antibody depressed MCP-1 release, and increased interleukin-12 production in dexamethasone-treated dendritic cells, thus demonstrating that interleukin-12 downregulation is largely dependent on MCP-1 overexpression. Our findings suggest that the induction of MCP expression in human dendritic cells by dexamethasone, and the amplification of cell response via the upregulation of the chemokine cognate receptor, may be critical to inhibit type 1 T-helper-biased immune response and, possibly, to favor type 2 T-helper-skewed response.
authors: Division of Nephrology and Dialysis, Department of Biomedical Sciences and Bioagromed, University of Foggia, Foggia, Italy.
authors: Leonarda
authors: L
authors: Roca
authors: Salvatore
authors: S
authors: Di Paolo
authors: Virna
authors: V
authors: Petruzzelli
authors: Giuseppe
authors: G
authors: Grandaliano
authors: Elena
authors: E
authors: Ranieri
authors: Francesco Paolo
authors: FP
authors: Schena
authors: Loreto
authors: L
authors: Gesualdo
mesh_terms: D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic / Q000235:genetics; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D018932:Chemokine CCL2; D054390:Receptors, CCR2; D018664:Interleukin-12; D003907:Dexamethasone