1. ¹Division of Nephrology and Dialysis, Department of Biomedical Sciences and Bioagromed, University of Foggia, Foggia, Italy
2. ²Division of Nephrology and Dialysis, Hospital 'Dimiccoli', Barletta, Italy
3. ³Division of Nephrology and Dialysis, Department of Emergency and Transplantation, University of Bari, Bari, Italy

Correspondence: Professor Loreto Gesualdo, Full Professor of Nephrology, Department of Biomedical Sciences–University of Foggia, V.le Pinto, 1, Foggia 71100, Italy. E-mail: l.gesualdo@unifg.it

Received 22 November 2006; Revised 20 June 2007; Accepted 2 July 2007; Published online 14 August 2007.

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-+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.