PMID- 26259605
OWN - NLM
STAT- MEDLINE
DCOM- 20160816
LR  - 20181113
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 148
IP  - 1
DP  - 2015 Nov
TI  - Aryl Hydrocarbon Receptor Activation Synergistically Induces 
      Lipopolysaccharide-Mediated Expression of Proinflammatory Chemokine (c-c motif) 
      Ligand 20.
PG  - 229-40
LID - 10.1093/toxsci/kfv178 [doi]
AB  - The Ah receptor (AHR) is directly involved in the regulation of both innate and 
      adaptive immunity. However, these activities are poorly understood at the level 
      of gene regulation. The chemokine (c-c motif) ligand 20 (CCL20) plays a 
      nonredundant role in the chemoattraction of C-C motif receptor 6 expressing cells 
      (eg, T cells and others). A survey of promoter regions of chemokine genes 
      revealed that there are several putative dioxin responsive elements in the mouse 
      Ccl20 promoter. The addition of an AHR agonist along with lipopolysaccharide 
      (LPS) to cultured primary peritoneal macrophages results in synergistic induction 
      of both Ccl20 mRNA and protein, compared with each compound alone. Through the 
      use of macrophage cultures derived from Ahr(-) (/) (-) and Ahr(nls/nls) mice, it 
      was established that expression of the AHR and its ability to translocate into 
      the nucleus are necessary for AHR ligand-mediated synergistic induction of Ccl20. 
      Gel shift analysis determined that a potent tandem AHR binding site ~3.1 kb 
      upstream from the transcriptional start site can efficiently bind the AHR/ARNT 
      (aryl hydrocarbon receptor/AHR nuclear translocator) heterodimer upon activation 
      with a number of AHR agonists. Furthermore, studies reveal that LPS increases AHR 
      levels on the Ccl20 promoter while decreasing HDAC1 occupancy. The level of Ccl20 
      constitutive expression in the colon is greatly attenuated in Ahr(-) (/) (-) 
      mice. These studies suggest that the presence of AHR ligands during localized 
      inflammation may augment chemokine expression, thus participating in the overall 
      response to pathogens.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the Society 
      of Toxicology. All rights reserved. For Permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Lahoti, Tejas S
AU  - Lahoti TS
AD  - Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology 
      and Carcinogenesis, Penn State University, University Park, Pennsylvania 16802.
FAU - Boyer, Jacob A
AU  - Boyer JA
AD  - Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology 
      and Carcinogenesis, Penn State University, University Park, Pennsylvania 16802.
FAU - Kusnadi, Ann
AU  - Kusnadi A
AD  - Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology 
      and Carcinogenesis, Penn State University, University Park, Pennsylvania 16802.
FAU - Muku, Gulsum E
AU  - Muku GE
AD  - Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology 
      and Carcinogenesis, Penn State University, University Park, Pennsylvania 16802.
FAU - Murray, Iain A
AU  - Murray IA
AD  - Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology 
      and Carcinogenesis, Penn State University, University Park, Pennsylvania 16802.
FAU - Perdew, Gary H
AU  - Perdew GH
AD  - Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology 
      and Carcinogenesis, Penn State University, University Park, Pennsylvania 16802 
      ghp2@psu.edu.
LA  - eng
GR  - R01 ES004869/ES/NIEHS NIH HHS/United States
GR  - ES004869/ES/NIEHS NIH HHS/United States
GR  - ES011699/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150810
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Ahr protein, mouse)
RN  - 0 (Arnt protein, mouse)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (CCL20 protein, mouse)
RN  - 0 (Carbazoles)
RN  - 0 (Chemokine CCL20)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
RN  - 241-55-4 (indolo(3,2-b)carbazole)
RN  - EC 3.5.1.98 (Hdac1 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Alleles
MH  - Animals
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism
MH  - Basic Helix-Loop-Helix Transcription Factors/agonists/genetics/*metabolism
MH  - Carbazoles/toxicity
MH  - Cells, Cultured
MH  - Chemokine CCL20/*agonists/genetics/metabolism
MH  - Crosses, Genetic
MH  - Drug Synergism
MH  - Environmental Pollutants/toxicity
MH  - Histone Deacetylase 1/antagonists & inhibitors/metabolism
MH  - Keratinocytes/cytology/*drug effects/metabolism
MH  - Ligands
MH  - Lipopolysaccharides/*agonists/toxicity
MH  - Macrophages, Peritoneal/cytology/*drug effects/immunology/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Mutant Strains
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Promoter Regions, Genetic/*drug effects
MH  - Receptors, Aryl Hydrocarbon/agonists/genetics/*metabolism
MH  - Up-Regulation/drug effects
PMC - PMC4731409
OTO - NOTNLM
OT  - AHR agonists
OT  - aryl hydrocarbon receptor
OT  - chemokine
OT  - chemokine (c-c motif)
OT  - ligand 20
OT  - lipopolysaccharide
OT  - macrophages
EDAT- 2015/08/12 06:00
MHDA- 2016/08/17 06:00
PMCR- 2016/11/01
CRDT- 2015/08/12 06:00
PHST- 2015/08/12 06:00 [entrez]
PHST- 2015/08/12 06:00 [pubmed]
PHST- 2016/08/17 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - kfv178 [pii]
AID - 10.1093/toxsci/kfv178 [doi]
PST - ppublish
SO  - Toxicol Sci. 2015 Nov;148(1):229-40. doi: 10.1093/toxsci/kfv178. Epub 2015 Aug 
      10.