The roles of Nrf2 and autophagy in modulating inflammation mediated by TLR4 - NFκB in A549 cell exposed to layer house particulate matter 2.5 (PM2.5). (November 2019)

• Record Type: Journal Article
• Authors: Dai, Pengyuan; Shen, Dan; Shen, Jiakun; Tang, Qian; Xi, Mengxue; Li, Yansen; Li, Chunmei
• Is Part Of: Chemosphere. Volume 235(2019)
• Page Start: 1134
• Page End: 1145
• Publication Date: 2019-11
• Subjects: PM2.5 -- Inflammation -- Nrf2 -- Oxidative stress -- Endoplasmic reticulum stress -- Autophagy; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2019.07.002
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Particulate matter (PM) from layer house has adverse effect on people and chicken respiratory health, which can further influence animal performance and reduce production efficiency. However, little study focus on the respiratory inflammation induced by PM2.5 from layer house and the underlying mechanism also unclear. In this study, human adenocarcinoma alveolar basal epithelial cells (A549 cell) was subjected to the PM2.5 from layer house to evaluate the inflammation reaction caused by PM2.5 and explore the role of Nrf2 and autophagy in regulating the inflammation. Results showed that the viability of A549 cell decreased in a time - and concentration - dependent manner after PM2.5 treatment. TNFα, IL6, and IL8 increased significantly treated with PM2.5 at 12 h. RNA sequencing indicated differentially expressed genes were enriched in immune system process, oxidative stress (OS), endoplasmic reticulum stress (ERS), and autophagy. Further studies showed TLR4 - NFκB p65 signal pathway involved in the inflammation reaction caused by PM2.5 . The overexpression of Nrf2 decreased the level of TNFα, IL6, IL8 markedly as well as the level of NFκB p65 and NFκB pp65. OS and ERS were also limited under overactivation of Nrf2 in PM2.5 treated cells. Autophagy induced by PM2.5 promoted the inflammation through increasing the level of NFκB p65 and NFκB pp65. Autophagy deficient strengthened the expression of Nrf2. Collectively, our study revealed Nrf2 prevents inflammation caused by layer house PM2.5 stimulation, however, autophagy exerts a promotive role in TLR4 - NFκB p65 mediating inflammation in A549 cell. Graphical abstract: Image 10577 Highlights: Layer house PM2.5 decreased cell viability and induced inflammation in A549 cells. TLR4 - NFκB signal pathway involved in the inflammation induced by PM2.5 in A549 cells. Nrf2 decreased PM2.5 - induced inflammation by inhibiting OS and ERS. Autophagy promoted PM2.5 - induced inflammation through enhancing the expression of NFκB p65 and NFκB pp65.