PMID- 20350561
OWN - NLM
STAT- MEDLINE
DCOM- 20100628
LR  - 20211020
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 246
IP  - 1-2
DP  - 2010 Jul
TI  - Functional and phenotypic effects of AhR activation in inflammatory dendritic 
      cells.
PG  - 18-28
LID - 10.1016/j.taap.2010.03.013 [doi]
AB  - Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin 
      (TCDD) induces immune suppression. Dendritic cells (DCs) are key antigen 
      presenting cells governing T cell activation and differentiation. However, the 
      consequences of AhR activation in DCs are not fully defined. We hypothesized that 
      AhR activation alters DC differentiation and generates dysfunctional DCs. To test 
      this hypothesis, inflammatory bone marrow-derived DCs (BMDCs) from C57Bl/6 mice 
      were generated in the presence of vehicle or TCDD. TCDD decreased CD11c 
      expression but increased MHC class II, CD86 and CD25 expression on the BMDCs. The 
      effects of TCDD were strictly AhR-dependent but not exclusively DRE-mediated. 
      Similar effects were observed with two natural AhR ligands, 
      6-formylindolo[3,2-b]carbazole (FICZ) and 
      2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid (ITE). TCDD increased LPS- 
      and CpG-induced IL-6 and TNF-alpha production by BMDCs but decreased their NO 
      production. TCDD decreased CpG-induced IL-12p70 production by BMDCs but did not 
      affect their secretion of IL-10. TCDD downregulated LPS- and CpG-induced NF-kB 
      p65 levels and induced a trend towards upregulation of RelB levels in the BMDCs. 
      AhR activation by TCDD modulated BMDC uptake of both soluble and particulate 
      antigens. Induction of indoleamine-2,3-dioxygenase (IDO) and TGF-beta3 has been 
      implicated in the generation of regulatory T cells following AhR activation. TCDD 
      increased IDO1, IDO2 and TGF-beta3 mRNA levels in BMDCs as compared to vehicle. 
      Despite the induction of regulatory mediators, TCDD-treated BMDCs failed to 
      suppress antigen-specific T cell activation. Thus, AhR activation can directly 
      alter the differentiation and innate functions of inflammatory DCs without 
      affecting their ability to successfully interact with T cells.
CI  - 2010 Elsevier Inc. All rights reserved.
FAU - Bankoti, Jaishree
AU  - Bankoti J
AD  - Department of Biomedical and Pharmaceutical Sciences, University of Montana, 
      Missoula, MT, USA.
FAU - Rase, Ben
AU  - Rase B
FAU - Simones, Tom
AU  - Simones T
FAU - Shepherd, David M
AU  - Shepherd DM
LA  - eng
GR  - P20 RR017670-040012/RR/NCRR NIH HHS/United States
GR  - R01 ES013784/ES/NIEHS NIH HHS/United States
GR  - RR017670/RR/NCRR NIH HHS/United States
GR  - RR015583/RR/NCRR NIH HHS/United States
GR  - P20 RR015583-09/RR/NCRR NIH HHS/United States
GR  - P20 RR017670/RR/NCRR NIH HHS/United States
GR  - R01 ES013784-03/ES/NIEHS NIH HHS/United States
GR  - P20 RR015583/RR/NCRR NIH HHS/United States
GR  - ES013784/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100327
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (NF-kappa B)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Dendritic Cells/chemistry/*drug effects/metabolism/physiology
MH  - Immunity, Innate/drug effects/physiology
MH  - Inflammation/physiopathology
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/analysis
MH  - Phenotype
MH  - Polychlorinated Dibenzodioxins/pharmacology
MH  - Receptors, Aryl Hydrocarbon/biosynthesis/*drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/drug effects
PMC - PMC2885531
MID - NIHMS193267
EDAT- 2010/03/31 06:00
MHDA- 2010/06/29 06:00
PMCR- 2011/07/01
CRDT- 2010/03/31 06:00
PHST- 2009/11/21 00:00 [received]
PHST- 2010/03/03 00:00 [revised]
PHST- 2010/03/18 00:00 [accepted]
PHST- 2010/03/31 06:00 [entrez]
PHST- 2010/03/31 06:00 [pubmed]
PHST- 2010/06/29 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - S0041-008X(10)00110-9 [pii]
AID - 10.1016/j.taap.2010.03.013 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2010 Jul;246(1-2):18-28. doi: 10.1016/j.taap.2010.03.013. 
      Epub 2010 Mar 27.