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microRNA-146a-5p negatively modulates PM2.5 caused inflammation in THP-1 cells via autophagy process

THP1细胞系 自噬 炎症 小RNA 细胞生物学 生物 化学 细胞培养 细胞凋亡 生物化学 免疫学 遗传学 基因
作者
Yu Shang,Qianyun Liu,Lu Wang,Xinghua Qiu,Yingjun Chen,Jing An
出处
期刊:Environmental Pollution [Elsevier BV]
卷期号:268: 115961-115961 被引量:11
标识
DOI:10.1016/j.envpol.2020.115961
摘要

Abstract Ambient fine particulate matter (PM2.5) can change the expression profile of microRNAs (miRs), which may play important roles in mediating inflammatory responses. The present study attempts to investigate the roles of miR-146a-5p in regulating cytokine expression in a human monocytic leukemia cell line (THP-1). Four types of PM2.5 extracts obtained from Beijing, China, were subjected to cytotoxic tests in THP-1 cells. These four PM2.5 extracts included two water extracts collected from non-heating and heating season (WN and WH), and two organic extracts from non-heating and heating season (DN and DH). Firstly, the four PM2.5 extracts caused cytotoxicity, oxidative stress responses, cytokine gene expressions and interleukin 8 (IL-8) release in THP-1 cells, with WH showing the highest cytotoxicity, WN showing the highest oxidative stress and inflammatory responses. Additionally, we observed expression of miR-146a-5p was significantly increased, with the maximal response of six folds in WN group. Cellular autophagy was initiated by PM2.5 indicated by related protein and gene expressions. Both RNA interference and autophagy inhibitor were applied to interrupt autophagy process in THP-1 cells. Autophagy dysfunction could alleviate IL-8 expression, suggesting autophagy process regulated cytokine expression and inflammatory response caused by PM2.5. A chemical inhibitor was applied to inhibit the function of miR-146a-5p, and then the expressions of IL-8 and autophagic genes were significantly aggravated. Meanwhile, two target genes of miR-146a-5p, interleukin-1 associated-kinase-1 (IRAK1) and tumor-necrosis factor receptor-associated factor-6 (TRAF6) were increased dramatically, which also played important roles in regulation of autophagy. These data suggested miR-146a-5p negatively modulated cytokine expression caused by PM2.5 via autophagy process through the target genes of IRAK1 and TRAF6. Our findings raised the concerns of the changes of miR expression profile and following responses caused by PM2.5.
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