PMID- 18270326
OWN - NLM
STAT- MEDLINE
DCOM- 20080916
LR  - 20240314
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 112
IP  - 4
DP  - 2008 Aug 15
TI  - Activation of the aryl hydrocarbon receptor is essential for mediating the 
      anti-inflammatory effects of a novel low-molecular-weight compound.
PG  - 1158-65
LID - 10.1182/blood-2007-08-109645 [doi]
AB  - VAF347 is a low-molecular-weight compound that inhibits allergic lung 
      inflammation in vivo. This effect is likely the result of a block of dendritic 
      cell (DC) function to generate proinflammatory T-helper (Th) cells because VAF347 
      inhibits interleukin (IL)-6, CD86, and human leukocyte antigen (HLA)-DR 
      expression by human monocyte-derived DC, 3 relevant molecules for Th-cell 
      generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon 
      receptor (AhR) protein, resulting in activation of the AhR signaling pathway. 
      Functional AhR is responsible for the biologic activity of VAF347 because (1) 
      other AhR agonists display an identical activity profile in vitro, (2) gene 
      silencing of wild-type AhR expression or forced overexpression of a 
      trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced 
      IL-6 expression in a human monocytic cell line, and (3) AhR-deficient mice are 
      resistant to the compound's ability to block allergic lung inflammation in vivo. 
      These data identify the AhR protein as key molecular target of VAF347 and its 
      essential role for mediating the anti-inflammatory effects of the compound in 
      vitro and in vivo.
FAU - Lawrence, B Paige
AU  - Lawrence BP
AD  - Department of Environmental Medicine, University of Rochester, NY, USA.
FAU - Denison, Michael S
AU  - Denison MS
FAU - Novak, Hermann
AU  - Novak H
FAU - Vorderstrasse, Beth A
AU  - Vorderstrasse BA
FAU - Harrer, Nathalie
AU  - Harrer N
FAU - Neruda, Wolfgang
AU  - Neruda W
FAU - Reichel, Claudia
AU  - Reichel C
FAU - Woisetschlager, Maximilian
AU  - Woisetschlager M
LA  - eng
GR  - R01 ES010619/ES/NIEHS NIH HHS/United States
GR  - K02 ES012409/ES/NIEHS NIH HHS/United States
GR  - R01 ES012498/ES/NIEHS NIH HHS/United States
GR  - R01-ES10619/ES/NIEHS NIH HHS/United States
GR  - R01-ES012498/ES/NIEHS NIH HHS/United States
GR  - K02-ES012409/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080212
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Interleukin-6)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (VAF347)
SB  - IM
CIN - Blood. 2008 Aug 15;112(4):928-9. PMID: 18684875
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal
MH  - Cell Line
MH  - Humans
MH  - Inflammation/drug therapy
MH  - Interleukin-6/antagonists & inhibitors/biosynthesis
MH  - Lung/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Weight
MH  - Monocytes
MH  - Pyrimidines/*pharmacology
MH  - Receptors, Aryl Hydrocarbon/*agonists
PMC - PMC2515129
EDAT- 2008/02/14 09:00
MHDA- 2008/09/17 09:00
PMCR- 2009/08/15
CRDT- 2008/02/14 09:00
PHST- 2008/02/14 09:00 [pubmed]
PHST- 2008/09/17 09:00 [medline]
PHST- 2008/02/14 09:00 [entrez]
PHST- 2009/08/15 00:00 [pmc-release]
AID - S0006-4971(20)49704-6 [pii]
AID - 2007/109645 [pii]
AID - 10.1182/blood-2007-08-109645 [doi]
PST - ppublish
SO  - Blood. 2008 Aug 15;112(4):1158-65. doi: 10.1182/blood-2007-08-109645. Epub 2008 
      Feb 12.