人原代脂肪细胞对 PCB126 的延迟性促炎反应依赖于芳香烃受体。
A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor.
机构信息
Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA, 52242, USA.
出版信息
Environ Sci Pollut Res Int. 2018 Jun;25(17):16481-16492. doi: 10.1007/s11356-017-9676-z. Epub 2017 Jul 11.
Abstract
Inflammation in adipose tissue is recognized as a causative factor in the development of type II diabetes. Adipocyte hypertrophy as well as bacterial and environmental factors have been implicated in causing inflammation in mature adipocytes. Exposure to persistent organic pollutants such as polychlorinated biphenyls (PCBs) has been associated with the development of type II diabetes. We show here that PCB126, a dioxin-like PCB, activates a robust proinflammatory state in fat cell precursors (preadipocytes). The response was found to be dependent on aryl hydrocarbon receptor (AhR) activation, although induction of the response was delayed compared to upregulation of CYP1A1, a classic AhR-responsive gene. Treatment of preadipocytes with a nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) inhibitor partially attenuated the PCB126-induced inflammatory response and partly, but not completely, ameliorated disruption of adipogenesis caused by PCB126. Our results indicate a role for PCB126 in mediating an inflammatory response through AhR in preadipocytes that interferes with adipogenesis.
摘要
脂肪组织中的炎症被认为是 II 型糖尿病发展的一个致病因素。脂肪细胞肥大以及细菌和环境因素都与成熟脂肪细胞中的炎症有关。接触持久性有机污染物，如多氯联苯（PCBs），与 II 型糖尿病的发展有关。我们在这里表明，二恶英样 PCB126 会激活脂肪细胞前体（前脂肪细胞）中的强烈促炎状态。该反应被发现依赖于芳烃受体（AhR）的激活，尽管与 CYP1A1 的上调相比，反应的诱导被延迟，CYP1A1 是一种经典的 AhR 反应基因。用核因子 kappa-轻链增强子的激活 B 细胞（NF-κB）抑制剂处理前脂肪细胞部分减弱了 PCB126 诱导的炎症反应，并部分但不完全改善了 PCB126 引起的脂肪生成破坏。我们的结果表明，PCB126 通过 AhR 在脂肪细胞前体中发挥作用，介导炎症反应，干扰脂肪生成。
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