Department of Child and Adolescent Health, School of Public Health, China Medical University, No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.
Department of Social Medicine, School of Public Health, China Medical University, No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, PR China.
Chemosphere. 2021 Apr;268:128837. doi: 10.1016/j.chemosphere.2020.128837. Epub 2020 Nov 6.
In previous studies we found that bisphenol A (BPA) aggravated OVA-induced lung inflammation. The aim of this research was to determine whether BPA exposure alone also induced inflammatory response in the lungs, which mechanism was associated with TLR4/NF-κB signaling pathway and the activation of mTOR-mediated autophagy. Female C57BL/6 mice aged 4 weeks were randomly divided into three groups (10/group): control group, 0.1 and 0.2 μg mL BPA groups. BPA induced the pathological changes in the lung and increased the levels of cytokines and inflammatory cells, as well as affected autophagy related proteins expression. In addition, the RAW264.7 cell culture experiment was conducted in order to confirm the role of autophagy. We found that BPA can enhance autophagy flux by enhancing autophagosome formation. It was further confirmed the details of the mechanism of action with chloroquine (CQ, a compound that inhibits the fusion of autophagosomes and lysosomes) intervention. The inhibition of autophagy led to down-regulation of expression levels associated with inflammation. This research results indicated that BPA induced inflammatory response in vitro and in vivo, and its mechanism may be related to TLR4/NF-κB signaling pathway and the activation of mTOR-mediated autophagy. After autophagy was suppressed, the inflammatory response also weakened. Our findings provide a new perspective into the mechanisms underlying inflammatory responses induced by the environmental exposure. These findings indicate that therapeutic strategies targeting autophagy may provide a new method for the treatment of inflammatory diseases.
在之前的研究中，我们发现双酚 A（BPA）加重了 OVA 诱导的肺部炎症。本研究旨在确定单独暴露于 BPA 是否也会引起肺部的炎症反应，其机制与 TLR4/NF-κB 信号通路和 mTOR 介导的自噬激活有关。4 周龄雌性 C57BL/6 小鼠随机分为三组（每组 10 只）：对照组、0.1 和 0.2μg/mL BPA 组。BPA 诱导肺部的病理变化，增加细胞因子和炎症细胞的水平，并影响自噬相关蛋白的表达。此外，还进行了 RAW264.7 细胞培养实验以验证自噬的作用。我们发现 BPA 可以通过增强自噬体形成来增强自噬流。进一步用氯喹（CQ，一种抑制自噬体和溶酶体融合的化合物）干预来证实作用机制的细节。自噬的抑制导致与炎症相关的表达水平下调。这些研究结果表明，BPA 可在体内和体外诱导炎症反应，其机制可能与 TLR4/NF-κB 信号通路和 mTOR 介导的自噬激活有关。自噬被抑制后，炎症反应也减弱。我们的研究结果为环境暴露引起的炎症反应的机制提供了新的视角。这些发现表明，针对自噬的治疗策略可能为炎症性疾病的治疗提供新的方法。
