Oncotarget

Research Papers:

Crucial role of pro-inflammatory cytokines from respiratory tract upon PM2.5 exposure in causing the BMSCs differentiation in cells and animals

Xiaoting Jin, Ruijun Su, Ruijin Li, Long Cheng and Zhuoyu Li _

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Oncotarget. 2018; 9:1745-1759. https://doi.org/10.18632/oncotarget.23158

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Abstract

Xiaoting Jin1, Ruijun Su2, Ruijin Li3, Long Cheng4 and Zhuoyu Li1,2

1Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China

2Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China

3Institute of Environmental Science, Shanxi University, Taiyuan, China

4Department of Neurology, Harvard Medical School, Boston, MA, USA

Correspondence to:

Zhuoyu Li, email: lzy@sxu.edu.cn

Keywords: PM2.5; BMSCs; inflammation; ROS; mitochondria

Received: September 08, 2017     Accepted: November 16, 2017     Published: December 11, 2017

ABSTRACT

Fine particulate matter exposure may cause health risk, including cardiovascular diseases and cancer. Bone marrow mesenchymal stem cell (BMSC), a typical model for evaluating pollutant toxicity, has been closely linked to these diseases, due to its characteristics of differentiation. We therefore studied the BMSCs differentiation and its roles in inflammatory activation in the respiratory tract upon PM2.5 exposure using both in vitro and in vivo models. BMSCs differentiation into endothelial-like cells (ELCs) and cancer-associated fibroblasts cells (CAFs) was enhanced in response to conditioned medium from PM2.5–treated 16HBE cells. PM2.5 elevated inflammatory cytokines’ expression and secretion in 16HBE cells. However, induction of differentiation markers was reduced when IL-1β, IL-6 and COX-2 neutralizing antibodies were added to the conditioned medium. Furthermore, PM2.5 induced ROS formation and NADPH oxidase (NOX) expression in 16HBE cells. DPI (inhibitor of ROS from NOX) or NAC (inhibitor of ROS) supplement reduced PM2.5-induced inflammatory activation and BMSCs differentiation. Likewise, a concomitant disorder of mitochondrial morphology and respiratory chain was observed. In addition, Rot or AA (inhibitor of mitochondrial complex I or III) supplement restored PM2.5-induced toxic effects. Moreover, the results coincided with the in vitro data obtained from SD rats post-exposed to different doses of PM2.5 for 30 days. PM2.5 enhanced the BMSCs differentiation and inflammatory cytokines’ expression in respiratory organs of SD rats, including lung and trachea tissue. This study uncovers that PM2.5 promotes the BMSCs differentiation via inflammatory activation mediated by ROS induction from NOX and mitochondria in the respiratory tract.


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