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KMID : 0613820210310121110
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Journal of Life Science
2021 Volume.31 No. 12 p.1110 ~ p.1119
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The Role of ROS-NF-κB Signaling Pathway in Enhancement of Inflammatory Response by Particulate Matter 2.5 in Lipopolysaccharide-stimulated RAW 264.7 Macrophages
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Kwon Da-Hye
Kim Da-Hye
Kim Min-Yeong
Hwangbo Hyun
Ji Seon-Yeong
Park Seh-Kwang
Jeong Ji-Won
Kim Mi-Young
Lee Hye-Sook
Cheong Jae-Hun
Nam Soo-Wan
Hwang Hye-Jin
Choi Yung-Hyun
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Abstract
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The purpose of this study was to investigate whether the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages could be promoted by particulate matter 2.5 (PM2.5) stimulation. To this end, the levels of inflammatory parameters, reactive oxygen species (ROS) and inflammation-regulating genes were investigated in RAW 264.7 cells treated with PM2.5 in the presence or absence of LPS. Our results showed that the production levels of pro-inflammatory mediators (nitric oxide and prostaglandin E2) and cytokines (interleukin-6 and -1β) were significantly increased by PM2.5 stimulation in LPS-treated RAW 264.7 cells, which was correlated with increased expression genes involved in their production. In addition, when LPS-treated RAW 264.7 cells were exposed to PM2.5, nuclear factor-kappaB (NF-κB) expression was further increased in the nucleus, and the expression of inhibitor of NF-κB as well as NF-κB in the cytoplasm was decreased. These results suggest that the co-treatment of PM2.5 and LPS further increases the activation of the NF-κB signaling pathway compared to each treatment alone, thereby contributing to the promotion of transcriptional activity of inflammatory genes. Furthermore, although the generation of ROS was greatly increased by PM2.5 in LPS-treated RAW 264.7 cells, the NF-κB inhibitor did not reduce the generation of ROS. In addition, when the generation of ROS was artificially suppressed, the production of inflammatory mediators and the activation of NF-κB were both abolished. Therefore, our results suggest that the increase in the NF-κB-mediated inflammatory response induced by PM2.5 in LPS-treated RAW 264.7 macrophages was a ROS generation-dependent phenomenon.
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KEYWORD
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Inflammation, lipopolysaccharide, NF-κB, Particulate matter 2.5, ROS
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