PM2.5 organic extract mediates inflammation through the ERβ pathway to contribute to lung carcinogenesis in vitro and vivo
PM2.5 organic extract mediates inflammation through the ERβ pathway to contribute to lung carcinogenesis in vitro and vivo
复制标题
PM2.5有机提取物通过ERb途径介导炎症，在体外和体内促进肺癌发生
DOI：
10.1016/j.chemosphere.2020.127867
复制
发表时间：
2021-01-01
期刊：
影响因子：
8.8
通讯作者：
Wang, Yan
中科院分区：
文献类型：
--
作者：
Luo, Fei;Guo, Huaqi;Wang, Yan
越来越多的研究表明，细颗粒物（PM2.5）与呼吸道炎症增加密切相关，甚至会导致肺癌。雌激素受体β（ER β）已被证明与几种癌症有关。然而，ERb在PM2.5有机提取物（Po）促进的炎症和肺癌中的确切作用仍然未知。本研究的目的是研究ER β是否参与Po诱导的炎症和肺癌。我们的体外研究结果表明，Po暴露后肺支气管上皮细胞中白细胞介素-6（IL-6）和ER β同时增加;此外，抑制ERb通过灭活ERK和AKT来减少IL-6的表达和分泌，进一步促进细胞恶性转化。此外，我们使用雌性C57 BL/6小鼠进行了吸入暴露于Po的动物模型。虽然我们无法在暴露于Po的小鼠中发现肿瘤组织，但我们检测到肺部炎症、上皮-间充质转化（EMT）表型和严重肺损伤的证据;此外，腹膜内注射PHTPP（一种ER β抑制剂）显示上述现象已得到改善，这证明Po刺激IL-6表达以促进炎症，EMT表型和通过ER β途径的肺损伤。总之，我们的研究结果证实了PM2.5的潜在毒性作用，并通过探索ER β调节炎症的机制增加了我们对PM2.5致癌潜力的理解。(C)2020爱思唯尔有限公司版权所有。
An increasing number of researches have shown that fine particulate matter (PM2.5) is closely related to increased respiratory inflammation and can even lead to lung cancer. Estrogen receptor beta (ER beta) has been demonstrated to be involved in several cancers. However, the exact role of ERb in PM2.5 organic extract (Po)-promoted inflammation and lung cancer remains unknown. The purpose of this study was to investigate whether ER beta is involved in Po induced inflammation and lung cancer. In vitro, our results showed that interleukin-6 (IL-6) and ER beta were simultaneously increased in lung bronchial epithelial cells exposed to Po; additionally, inhibition of ERb decreased IL-6 expression and secretion through inactivating ERK and AKT and further promoted cells malignant transformation. Moreover, we performed an animal model of inhalation exposure to Po using female C57BL/6 mice. Although we were unable to find tumor tissue in mice exposed to Po, we detected evidence of lung inflammation, epithelial-tomesenchymal transition (EMT) phenotype and severe pulmonary injury; in addition, intraperitoneal injection of PHTPP (an ER beta inhibitor) showed that the above phenomena have been improved, which demonstrate that Po stimulates IL-6 expression to promote inflammation, EMT phenotype and lung injury through the ER beta pathway. In conclusion, our results confirmed the potential toxic effect of PM2.5, and increased our understanding of PM2.5 carcinogenic potential by exploring the mechanism of ER beta regulating inflammation. (C) 2020 Elsevier Ltd. All rights reserved.