PCB 126 induces monocyte/macrophage polarization and inflammation through AhR and NF-κB pathways

Chunyan Wang, Michael C. Petriello, Beibei Zhu, Bernhard Hennig

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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 TNFα and IL-1β, 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-κB antagonists prior to PCB treatment. The NF-κB 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.

Original languageEnglish
Pages (from-to)71-81
Number of pages11
JournalToxicology and Applied Pharmacology
Volume367
DOIs
StatePublished - Mar 15 2019

Bibliographical note

Funding Information:
Research reported in this publication was supported in part by the National Institute of Environmental Health Sciences at the National Institutes of Health [ P42ES007380 ], Michael C. Petriello was supported by National Institutes of Health [ K99ES028734 ].

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Atherosclerosis
  • Cardiovascular disease
  • Dioxins
  • Inflammation
  • Monocyte macrophage polarization
  • PCB 126

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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