The environmental obesogen bisphenol A increases macrophage self-renewal

• Published in: Cell and tissue research 2019-10, Vol.378 (1), p.81-96
• Main Authors: Ampem, Grace, Junginger, Alexandra, Yu, Haidong, Balogh, Lajos, Thuróczy, Julianna, Schneider, Marion E., Röszer, Tamás
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - immunology; Air Pollutants, Occupational - toxicity; Animals; Benzhydryl Compounds - toxicity; Biomedical and Life Sciences; Biomedicine; Bisphenol A; Cell activation; Cell Self Renewal - drug effects; Comparative analysis; Endocrine disruptors; Endocrine Disruptors - toxicity; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Human Genetics; Liver; Liver X receptors; Liver X Receptors - metabolism; Macrophages; Macrophages - drug effects; Macrophages - physiology; Male; Mice; Mice, Inbred C57BL; Molecular Medicine; Neurophysiology; Obesity; Obesity - chemically induced; Obesity - immunology; Phenols; Phenols - toxicity; Phosphorylation; Proteomics; Regular Article; Type 2 diabetes
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-019-03019-5

Self-renewal of macrophages is important for the healthy development and replenishment of tissue-resident macrophage pools. How this mechanism is controlled by endocrine signals is still largely unexplored. Here, we show that the endocrine disruptor bisphenol A (BPA) increases macrophage self-renewal. This effect was associated with phosphorylation of extracellular signal-regulated kinase (ERK) and a slight increase in the expression of liver X receptor alpha (LXRα). We found that LXRα inhibition induced, while LXRα activation impeded, macrophage self-renewal. LXRα signaling hence may protect from excessive macrophage expansion. Self-renewing macrophages, however, had negligible LXRα expression when compared with quiescent macrophages. Accordingly, tissue-resident macrophage pools, which are dominated by quiescent macrophages, were rich in LXRα-expressing macrophages. Overall, we show that BPA increases macrophage self-renewal and that this effect, at least in part, can be inhibited by increasing LXRα expression. Since BPA is accumulated in the adipose tissue, it has the potential to increase self-renewal of adipose tissue macrophages, leading to a condition that might negatively impact adipose tissue health.