PMID- 23430108
OWN - NLM
STAT- MEDLINE
DCOM- 20130628
LR  - 20211108
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 121
IP  - 15
DP  - 2013 Apr 11
TI  - Aryl hydrocarbon receptor contributes to the MEK/ERK-dependent maintenance of the 
      immature state of human dendritic cells.
PG  - e108-17
LID - 10.1182/blood-2012-07-445106 [doi]
AB  - Dendritic cells (DCs) promote tolerance or immunity depending on their maturation 
      state, which is enhanced or accelerated upon MEK-ERK signaling pathway 
      inhibition. We have determined the contribution of MEK-ERK activation to the 
      profile of gene expression of human immature monocyte-derived dendritic cells 
      (MDDCs) and peripheral blood myeloid DCs. ERK inhibition altered the expression 
      of genes that mediate Chemokine (C-C motif) ligand 19 (CCL19)-directed migration 
      (CCR7) and low-density lipoprotein (LDL) binding (CD36, SCARB1, OLR1, CXCL16) by 
      immature DCs. In addition, ERK upregulated CCL2 expression while impairing the 
      expression of DC maturation markers (RUNX3, ITGB7, IDO1). MEK-ERK-regulated genes 
      exhibited an overrepresentation of cognate sequences for the aryl hydrocarbon 
      receptor (AhR) transcription factor, whose transcriptional and DNA-binding 
      activities increased in MDDCs upon exposure to the MEK1/2 inhibitor U0126. 
      Therefore, the MEK-ERK signaling pathway regulates antigen capture, lymph node 
      homing, and acquisition of maturation-associated genes, and its contribution to 
      the maintenance of the immature state of MDDCs and myeloid DCs is partly 
      dependent on the activity of AhR. Since pharmacologic modulation of the MEK-ERK 
      signaling pathway has been proposed as a potential therapeutic strategy for 
      cancer, our findings indicate that ERK inhibitors might influence antitumor 
      responses through regulation of critical DC effector functions.
FAU - Aguilera-Montilla, Noemi
AU  - Aguilera-Montilla N
AD  - Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones 
      Cientificas (CSIC), Madrid, Spain.
FAU - Chamorro, Sonia
AU  - Chamorro S
FAU - Nieto, Concha
AU  - Nieto C
FAU - Sanchez-Cabo, Fatima
AU  - Sanchez-Cabo F
FAU - Dopazo, Ana
AU  - Dopazo A
FAU - Fernandez-Salguero, Pedro Maria
AU  - Fernandez-Salguero PM
FAU - Rodriguez-Fernandez, Jose Luis
AU  - Rodriguez-Fernandez JL
FAU - Pello, Oscar M
AU  - Pello OM
FAU - Andres, Vicente
AU  - Andres V
FAU - Cuenda, Ana
AU  - Cuenda A
FAU - Alonso, Barbara
AU  - Alonso B
FAU - Dominguez-Soto, Angeles
AU  - Dominguez-Soto A
FAU - Sanchez-Ramon, Silvia
AU  - Sanchez-Ramon S
FAU - Corbi, Angel L
AU  - Corbi AL
LA  - eng
SI  - GEO/GSE39745
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130221
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Butadienes)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Core Binding Factor Alpha 3 Subunit)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (IDO1 protein, human)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitriles)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Runx3 protein, human)
RN  - 0 (U 0126)
RN  - EC 2.7.11.24 (MAPK1 protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Blotting, Western
MH  - Butadienes/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Core Binding Factor Alpha 3 Subunit/genetics/metabolism
MH  - Dendritic Cells/drug effects/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression/drug effects
MH  - Gene Expression Profiling
MH  - Hep G2 Cells
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/genetics/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/genetics/*metabolism
MH  - Monocytes/drug effects/metabolism
MH  - Nitriles/pharmacology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Polychlorinated Dibenzodioxins/pharmacology
MH  - Receptors, Aryl Hydrocarbon/genetics/*metabolism
MH  - Receptors, CCR7/genetics/metabolism
EDAT- 2013/02/23 06:00
MHDA- 2013/07/03 06:00
CRDT- 2013/02/23 06:00
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
AID - S0006-4971(20)49822-2 [pii]
AID - 10.1182/blood-2012-07-445106 [doi]
PST - ppublish
SO  - Blood. 2013 Apr 11;121(15):e108-17. doi: 10.1182/blood-2012-07-445106. Epub 2013 
      Feb 21.