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Int. J. Mol. Sci. 2017, 18(7), 1484; doi:10.3390/ijms18071484

Autophagy Induced FHL2 Upregulation Promotes IL-6 Production by Activating the NF-κB Pathway in Mouse Aortic Endothelial Cells after Exposure to PM2.5

Laboratory of Genomic Engineering, Beijing Institute of Basic Medical Sciences, Beijing 100000, China
Institute for Environmental Health and Related Product Safety, Chinese center for disease control, Beijing 100000, China
Authors to whom correspondence should be addressed.
Received: 6 June 2017 / Revised: 30 June 2017 / Accepted: 7 July 2017 / Published: 17 July 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Epidemiological and clinical studies have increasingly shown that fine particulate matter (PM2.5) is associated with cardiovascular morbidity and mortality, which share the common feature of PM2.5-induced vascular inflammation; however, the underlying mechanisms of how PM2.5 triggers increased inflammatory response in vascular endothelial cells are not well understood. After treating mouse aortic endothelial cells (MAECs) with different concentrations of PM2.5, we assessed interleukin (IL)-6 and four and a half LIM domains 2 (FHL2) expression in cell supernatant by enzyme-linked immunosorbent assay and Western blot, respectively, as well as activation of nuclear factor (NF)-κB and immune-response signaling pathways. Additionally, changes in pathway activation, IL-6 expression, and autophagy were evaluated under PM2.5 exposure, following FHL2 knockdown with small interfering RNA. Our results indicated that PM2.5 exposure induced FHL2 expression and IL-6 secretion, as well as activation of pathways associated with immune response. Additionally, following FHL2 knockdown, the activation of NF-κB-related pathways and IL-6 secretion was inhibited under PM2.5 exposure, although the Akt- and p38-signaling pathways were not affected. Furthermore, PM2.5 exposure induced autophagy, whereas autophagy inhibition eventually inhibited PM2.5-induced FHL2 expression. These findings suggested a novel link between autophagy induced FHL2 upregulation and IL-6 production in MAECs under PM2.5 exposure. View Full-Text
Keywords: PM2.5; FHL2; IL-6; NF-κB; autophagy; mouse aortic endothelial cells PM2.5; FHL2; IL-6; NF-κB; autophagy; mouse aortic endothelial cells

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Xia, W.-R.; Fu, W.; Wang, Q.; Zhu, X.; Xing, W.-W.; Wang, M.; Xu, D.-Q.; Xu, D.-G. Autophagy Induced FHL2 Upregulation Promotes IL-6 Production by Activating the NF-κB Pathway in Mouse Aortic Endothelial Cells after Exposure to PM2.5. Int. J. Mol. Sci. 2017, 18, 1484.

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