Journal article
Polychlorinated biphenyls induce immunometabolic switch of anti-inflammatory macrophages toward an inflammatory phenotype
PNAS nexus, Vol.4(4), pgaf100
04/2025
DOI: 10.1093/pnasnexus/pgaf100
PMCID: PMC11969150
PMID: 40191133
Abstract
Polychlorinated biphenyls (PCBs) are a group of environmental toxicants associated with increased risk of diabetes, obesity, and metabolic syndrome. These metabolic disorders are characterized by systemic and local inflammation within adipose tissue, the primary site of PCB accumulation. These inflammatory changes arise when resident adipose tissue macrophages undergo phenotypic plasticity – switching from an anti-inflammatory to an inflammatory phenotype. Thus, we sought to assess whether PCB exposure drives macrophage phenotypic switching. We investigated how human monocyte-derived macrophages polarized toward an M1, M2a, or M2c phenotype were impacted by exposure to Aroclor 1254, a PCB mixture found at high levels in school air. We showed that PCB exposure not only exacerbates the inflammatory phenotype of M1 macrophages but also shifts both M2a and M2c cells toward a more inflammatory phototype in both a dose- and time-dependent manner. Additionally, we show that PCB exposure leads to significant metabolic changes. M2 macrophages exposed to PCBs exhibit increased reliance on aerobic glycolysis and reduced capacity for fatty acid and amino acid oxidation—both indicators of an inflammatory macrophage phenotype. Collectively, these results demonstrate that PCBs promote immunometabolic macrophage plasticity toward a more M1-like phenotype, thereby suggesting that PCBs exacerbate metabolic diseases by altering the inflammatory environment in adipose tissue.
Details
- Title: Subtitle
- Polychlorinated biphenyls induce immunometabolic switch of anti-inflammatory macrophages toward an inflammatory phenotype
- Creators
- Riley M Behan-Bush - University of IowaMichael V Schrodt - University of IowaElizabeth Kilburg - University of IowaJesse N Liszewski - University of IowaLaura M BitterlichKaren EnglishAloysius J Klingelhutz - University of IowaJames A Ankrum - University of Iowa
- Resource Type
- Journal article
- Publication Details
- PNAS nexus, Vol.4(4), pgaf100
- DOI
- 10.1093/pnasnexus/pgaf100
- PMID
- 40191133
- PMCID
- PMC11969150
- NLM abbreviation
- PNAS Nexus
- ISSN
- 2752-6542
- eISSN
- 2752-6542
- Publisher
- OXFORD UNIV PRESS
- Grant note
- NIEHS: P42ES013661 NIGMS: T32GM139776, F30ES035622 NCI: P30CA086862 University of Iowa Carver College of Medicine
This study was supported by the NIEHS P42ES013661 (J.A.A. and A.J.K.). R.M.B.-.B was supported by the NIGMS T32GM139776, and NIEHS F30ES035622. The TPC was supported by NCI P30CA086862 and the University of Iowa Carver College of Medicine.
- Language
- English
- Electronic publication date
- 03/27/2025
- Date published
- 04/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Iowa Technology Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Iowa Superfund Research Program; Internal Medicine
- Record Identifier
- 9984803812102771
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