PMID- 30768972
OWN - NLM
STAT- MEDLINE
DCOM- 20191219
LR  - 20200315
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 367
DP  - 2019 Mar 15
TI  - PCB 126 induces monocyte/macrophage polarization and inflammation through AhR and 
      NF-kappaB pathways.
PG  - 71-81
LID - S0041-008X(19)30055-9 [pii]
LID - 10.1016/j.taap.2019.02.006 [doi]
AB  - Polychlorinated biphenyls (PCBs) are persistent organic pollutants that 
      contribute to inflammatory diseases such as atherosclerosis, and macrophages play 
      a key role in the overall inflammatory response. Depending on specific 
      environmental stimuli, macrophages can be polarized either to pro-inflammatory 
      (e.g., M1) or anti-inflammatory (e.g., M2) phenotypes. We hypothesize that 
      dioxin-like PCBs can contribute to macrophage polarization associated with 
      inflammation. To test this hypothesis, human monocytes (THP-1) were 
      differentiated to macrophages and subsequently exposed to PCB 126. Exposure to 
      PCB 126, but not to PCB 153 or 118, significantly induced the expression of 
      inflammatory cytokines, including TNFalpha and IL-1beta, suggesting polarization to the 
      pro-inflammatory M1 phenotype. Additionally, monocyte chemoattractant protein-1 
      (MCP-1) was increased in PCB 126-activated macrophages, suggesting induction of 
      chemokines which regulate immune cell recruitment and infiltration of 
      monocytes/macrophages into vascular tissues. In addition, oxidative stress 
      sensitive markers including nuclear factor (erythroid-derived 2)-like 2 (NFE2L2; 
      Nrf2) and down-stream genes, such as heme oxygenase 1 (HMOX1) and NAD(P)H quinone 
      oxidoreductase 1 (NQO1), were induced following PCB 126 exposure. Since 
      dioxin-like PCBs may elicit inflammatory cascades through multiple mechanisms, we 
      then pretreated macrophages with both aryl hydrocarbon receptor (AhR) and NF-kappaB 
      antagonists prior to PCB treatment. The NF-kappaB antagonist BMS-345541 significantly 
      decreased mRNA and protein levels of multiple cytokines by approximately 50% 
      compared to PCB treatment alone, but the AhR antagonist CH-223191 was protective 
      to a lesser degree. Our data demonstrate the involvement of PCB 126 in macrophage 
      polarization and inflammation, indicating another important role of dioxin-like 
      PCBs in the pathology of atherosclerosis.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Wang, Chunyan
AU  - Wang C
AD  - University of Kentucky Superfund Research Center, University of Kentucky, 
      Lexington, KY, USA.
FAU - Petriello, Michael C
AU  - Petriello MC
AD  - University of Kentucky Superfund Research Center, University of Kentucky, 
      Lexington, KY, USA; Cardiovascular Medicine, University of Kentucky, Lexington, 
      KY, USA.
FAU - Zhu, Beibei
AU  - Zhu B
AD  - Department of Internal Medicine, Division of Endocrinology, Barnstable Brown 
      Diabetes and Obesity Center, University of Kentucky, Lexington, KY, USA.
FAU - Hennig, Bernhard
AU  - Hennig B
AD  - University of Kentucky Superfund Research Center, University of Kentucky, 
      Lexington, KY, USA; Department of Animal and Food Sciences, University of 
      Kentucky, Lexington, KY, USA. Electronic address: bhennig@uky.edu.
LA  - eng
GR  - K99 ES028734/ES/NIEHS NIH HHS/United States
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190213
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (AHR protein, human)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 2B2AQE8U50 (2,3',4,4',5-pentachlorobiphenyl)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl)
RN  - ZRU0C9E32O (2,4,5,2',4',5'-hexachlorobiphenyl)
SB  - IM
MH  - Basic Helix-Loop-Helix Transcription Factors/*agonists/metabolism
MH  - Cell Differentiation/*drug effects
MH  - Cytokines/*metabolism
MH  - Humans
MH  - Inflammation/*chemically induced/metabolism/pathology
MH  - Inflammation Mediators/*metabolism
MH  - Macrophages/*drug effects/metabolism/pathology
MH  - NF-kappa B/*metabolism
MH  - Phenotype
MH  - Polychlorinated Biphenyls/*toxicity
MH  - Receptors, Aryl Hydrocarbon/*agonists/metabolism
MH  - Signal Transduction/drug effects
MH  - THP-1 Cells
PMC - PMC6402591
MID - NIHMS1521951
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Cardiovascular disease
OT  - Dioxins
OT  - Inflammation
OT  - Monocyte macrophage polarization
OT  - PCB 126
EDAT- 2019/02/16 06:00
MHDA- 2019/12/20 06:00
PMCR- 2020/03/15
CRDT- 2019/02/16 06:00
PHST- 2018/09/28 00:00 [received]
PHST- 2019/01/25 00:00 [revised]
PHST- 2019/02/11 00:00 [accepted]
PHST- 2019/02/16 06:00 [pubmed]
PHST- 2019/12/20 06:00 [medline]
PHST- 2019/02/16 06:00 [entrez]
PHST- 2020/03/15 00:00 [pmc-release]
AID - S0041-008X(19)30055-9 [pii]
AID - 10.1016/j.taap.2019.02.006 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2019 Mar 15;367:71-81. doi: 10.1016/j.taap.2019.02.006. 
      Epub 2019 Feb 13.