Work

Polychlorinated biphenyls induce macrophage immunometabolic plasticity 2371

Year: 2025

Type: article

Abstract: Description We investigated whether exposure to polychlorinated biphenyls (PCBs) induces macrophage phenotypic switching toward an inflammatory phenotype. Human exposure to PCBs, an environmental toxicant, has been linked to an increased risk of diabetes, obesity, and metabolic syndrome. Despite the key role of adipose macrophages in metabolic disease and the known accumulation of PCBs in adipose, little is known about how PCBs impact macrophages. Here, we exposed anti-inflammatory macrophages (i.e. polarized with IL-4 or dexamethasone) to PCBs and then profiled phenotypic shifts by assessing surface marker expression, protein secretion, and energy metabolism. Our results show that PCB-exposed macrophages exhibited decreased expression of anti-inflammatory surface markers CD163 and CD206, while expression of inflammatory marker CD86 remained unchanged. PCB exposure also resulted in a marked 400x-1000x increase in the inflammatory cytokine IL-8 as well as a significant reduction in the anti-inflammatory cytokine IL-10. Additionally, we found that PCB-exposed cells had a greater dependence on aerobic glycolysis and a reduced ability to utilize fatty acid and amino acid oxidation as fuel – both metabolic features of more inflammatory macrophages. Collectively, these results demonstrate that PCBs promote macrophage plasticity toward a more inflammatory phenotype. More broadly, our work suggests that PCBs amplify metabolic diseases by altering the inflammatory environment of adipose tissue. Funding Sources Supported by NIH P42 ES01366; NIH F30 ES035622; NIH T32 GM139776. Topic Categories Immune Mechanisms of Human Disease (HUM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.297