PMID- 12181450
OWN - NLM
STAT- MEDLINE
DCOM- 20020905
LR  - 20190607
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 62
IP  - 3
DP  - 2002 Sep
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-alpha and 
      anti-CD40-induced activation of NF-kappaB/Rel in dendritic cells: p50 homodimer 
      activation is not affected.
PG  - 722-8
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses many immune responses, both 
      innate and adaptive. Suppression is mediated by the aryl hydrocarbon receptor 
      (AhR), a ligand-activated transcription factor. The AhR mediates TCDD toxicity 
      presumably through the alteration of transcriptional events, either by promoting 
      gene expression or potentially by physically interacting with other transcription 
      factors. Another transcription factor, NF-kappaB/Rel, is involved in several 
      signaling pathways in immune cells and is crucial for generating effective immune 
      responses. Dendritic cells (DCs), considered to be the "pacemakers" of the immune 
      system, were recently recognized as targets of TCDD and are also dependent on 
      NF-kappaB/Rel for activation and survival. In these studies, we investigated 
      whether TCDD would alter the activation of NF-kappaB/Rel in DCs. The dendritic 
      cell line DC2.4 was exposed to TCDD before treatment with tumor necrosis factor 
      alpha (TNF-alpha) or anti-CD40, and NF-kappaB/Rel activation was measured by 
      electrophoretic mobility shift assay and immunoblotting. TCDD suppressed the 
      binding of NF-kappaB/Rel to its cognate response element in TNF-alpha- and 
      anti-CD40-treated cells and blocked translocation to the nucleus. The AhR was 
      shown to associate with RelA, after coimmunoprecipitation, and seemed to block 
      its binding to DNA. It is noteworthy that p50 homodimers freely bound to DNA. 
      These results suggest that TCDD may alter the balance between NF-kappaB/Rel 
      heterodimers and transcriptional inhibitory p50 homodimers in DCs, leading to 
      defects in the DCs and suppression of the immune response.
FAU - Ruby, Carl E
AU  - Ruby CE
AD  - Department of Environmental and Molecular Toxicology, and Environmental Health 
      Science Center, Oregon State University, Corvallis, Oregon 97331, USA.
FAU - Leid, Mark
AU  - Leid M
FAU - Kerkvliet, Nancy I
AU  - Kerkvliet NI
LA  - eng
GR  - ES00040/ES/NIEHS NIH HHS/United States
GR  - ES00210/ES/NIEHS NIH HHS/United States
GR  - ES07060/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Antibodies)
RN  - 0 (CD40 Antigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Oncogene Proteins v-rel)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Teratogens)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Animals
MH  - Antibodies/immunology
MH  - Binding Sites
MH  - CD40 Antigens/immunology
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/metabolism
MH  - Dendritic Cells/*drug effects/metabolism
MH  - *I-kappa B Proteins
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - Oncogene Proteins v-rel/metabolism
MH  - Peptide Hydrolases/metabolism
MH  - Phosphorylation/drug effects
MH  - Polychlorinated Dibenzodioxins/*pharmacology
MH  - Protein Binding
MH  - Receptors, Aryl Hydrocarbon/metabolism
MH  - Teratogens/*pharmacology
MH  - Transcription Factor RelA
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2002/08/16 10:00
MHDA- 2002/09/06 10:01
CRDT- 2002/08/16 10:00
PHST- 2002/08/16 10:00 [pubmed]
PHST- 2002/09/06 10:01 [medline]
PHST- 2002/08/16 10:00 [entrez]
AID - 10.1124/mol.62.3.722 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2002 Sep;62(3):722-8. doi: 10.1124/mol.62.3.722.