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低分子量多环芳烃通过激活PI3K/AKT和NF-κB信号通路诱导A549细胞发生炎症。

Low molecular weight-PAHs induced inflammation in A549 cells by activating PI3K/AKT and NF-κB signaling pathways.

作者信息

Guo Huizhen, Huang Yushan, Wang Huiling, Zhang Zhewen, Li Chengyun, Hu Fengjing, Zhang Wenwen, Liu Yang, Zeng Yong, Wang Junling

机构信息

Department of Toxicology, School of Public Health, Lanzhou University, No. 199 Donggang West Road, Lanzhou 730000, Gansu, China.

Department of Integrated Chinese and Western Medicine Gynecology, Gansu Provincial Maternity and Child-care Hospital, No. 143 Qilihe North Street, Lanzhou 730000, Gansu, China.

出版信息

Toxicol Res (Camb). 2021 Jan 25;10(1):150-157. doi: 10.1093/toxres/tfaa105. eCollection 2021 Jan.

Abstract

Our previous study has demonstrated that two low molecular weight-polycyclic aromatic hydrocarbons (LMW-PAHs), phenanthrene (Phe) and fluorene (Flu), alone and as a mixture could induce oxidative damage and inflammation in A549 cells. However, the associated mechanisms have not been well discussed. The aim of this study was to further investigate the roles of PI3K/AKT and NF-κB signaling pathways in the inflammatory effects in A549 cells induced by Phe, Flu and their mixture. The results indicated that Phe, Flu and their mixture significantly activated PI3K/AKT and NF-κB signaling pathways by increasing the phosphorylation levels of PI3K, AKT, IκBα and NF-κB p65. In addition, pro-inflammatory cytokine expressions of TNF-α and IL-6 induced by the binary mixture of Phe and Flu were all alleviated by co-treatment with PI3K/AKT and NF-κB specific inhibitors (LY294002 and BAY11-7082). The results suggested that PI3K/AKT and NF-κB signaling pathways played an important role in LMW-PAHs induced inflammation in A549 cells.

摘要

我们之前的研究表明,两种低分子量多环芳烃(LMW-PAHs),菲(Phe)和芴(Flu),单独及混合存在时均可诱导A549细胞发生氧化损伤和炎症。然而,相关机制尚未得到充分探讨。本研究的目的是进一步研究PI3K/AKT和NF-κB信号通路在Phe、Flu及其混合物诱导的A549细胞炎症效应中的作用。结果表明,Phe、Flu及其混合物通过增加PI3K、AKT、IκBα和NF-κB p65的磷酸化水平,显著激活了PI3K/AKT和NF-κB信号通路。此外,Phe和Flu二元混合物诱导的TNF-α和IL-6促炎细胞因子表达,在与PI3K/AKT和NF-κB特异性抑制剂(LY294002和BAY11-7082)共同处理后均得到缓解。结果表明,PI3K/AKT和NF-κB信号通路在LMW-PAHs诱导的A549细胞炎症中起重要作用。

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