PMID- 17700511
OWN - NLM
STAT- MEDLINE
DCOM- 20080215
LR  - 20180822
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 85
IP  - 8
DP  - 2007 Nov-Dec
TI  - Dexamethasone modulates interleukin-12 production by inducing monocyte 
      chemoattractant protein-1 in human dendritic cells.
PG  - 610-6
AB  - 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.
FAU - Roca, Leonarda
AU  - Roca L
AD  - Division of Nephrology and Dialysis, Department of Biomedical Sciences and 
      Bioagromed, University of Foggia, Foggia, Italy.
FAU - Di Paolo, Salvatore
AU  - Di Paolo S
FAU - Petruzzelli, Virna
AU  - Petruzzelli V
FAU - Grandaliano, Giuseppe
AU  - Grandaliano G
FAU - Ranieri, Elena
AU  - Ranieri E
FAU - Schena, Francesco Paolo
AU  - Schena FP
FAU - Gesualdo, Loreto
AU  - Gesualdo L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070814
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 187348-17-0 (Interleukin-12)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Dendritic Cells/*drug effects/*metabolism
MH  - Dexamethasone/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Interleukin-12/*biosynthesis
MH  - Promoter Regions, Genetic/genetics
MH  - Receptors, CCR2/genetics/metabolism
MH  - Transfection
EDAT- 2007/08/19 09:00
MHDA- 2008/02/19 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2008/02/19 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - 7100108 [pii]
AID - 10.1038/sj.icb.7100108 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2007 Nov-Dec;85(8):610-6. doi: 10.1038/sj.icb.7100108. Epub 
      2007 Aug 14.