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Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes

Subacute poisoning of 1,2-dichloroethane (1,2-DCE) has become a serious occupational problem in China, and brain edema is its main pathological consequence, but little is known about the underlying mechanisms. As the metabolite of 1,2-DCE, 2-chloroethanol (2-CE) is more reactive, and might play an i...

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Autores principales: Wang, Tong, Jin, Xiaoxia, Liao, Yingjun, Sun, Qi, Luo, Chaohong, Wang, Gaoyang, Zhao, Fenghong, Jin, Yaping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115792/
https://www.ncbi.nlm.nih.gov/pubmed/30087244
http://dx.doi.org/10.3390/cells7080096
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author Wang, Tong
Jin, Xiaoxia
Liao, Yingjun
Sun, Qi
Luo, Chaohong
Wang, Gaoyang
Zhao, Fenghong
Jin, Yaping
author_facet Wang, Tong
Jin, Xiaoxia
Liao, Yingjun
Sun, Qi
Luo, Chaohong
Wang, Gaoyang
Zhao, Fenghong
Jin, Yaping
author_sort Wang, Tong
collection PubMed
description Subacute poisoning of 1,2-dichloroethane (1,2-DCE) has become a serious occupational problem in China, and brain edema is its main pathological consequence, but little is known about the underlying mechanisms. As the metabolite of 1,2-DCE, 2-chloroethanol (2-CE) is more reactive, and might play an important role in the toxic effects of 1,2-DCE. In our previous studies, we found that matrix metalloproteinases-9 (MMP-9) expression was enhanced in mouse brains upon treatment with 1,2-DCE, and in rat astrocytes exposed to 2-CE. In the present study, we analyzed the association of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) with MMP-9 overexpression in astrocytes treated with 2-CE. MMP-9, p65, c-Jun, and c-Fos were significantly upregulated by 2-CE treatment, which also enhanced phosphorylation of c-Jun, c-Fos and inhibitor of κBα (IκBα), and nuclear translocation of p65. Furthermore, inhibition of IκBα phosphorylation and AP-1 activity with the specific inhibitors could attenuate MMP-9 overexpression in the cells. On the other hand, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway suppressed the activation of both NF-κB and AP-1 in 2-CE-treated astrocytes. In conclusion, MMP-9 overexpression induced by 2-CE in astrocytes could be mediated at least in part through the p38 signaling pathway via activation of both NF-κB and AP-1. This study might provide novel clues for clarifying the mechanisms underlying 1,2-DCE associated cerebral edema.
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spelling pubmed-61157922018-08-31 Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes Wang, Tong Jin, Xiaoxia Liao, Yingjun Sun, Qi Luo, Chaohong Wang, Gaoyang Zhao, Fenghong Jin, Yaping Cells Article Subacute poisoning of 1,2-dichloroethane (1,2-DCE) has become a serious occupational problem in China, and brain edema is its main pathological consequence, but little is known about the underlying mechanisms. As the metabolite of 1,2-DCE, 2-chloroethanol (2-CE) is more reactive, and might play an important role in the toxic effects of 1,2-DCE. In our previous studies, we found that matrix metalloproteinases-9 (MMP-9) expression was enhanced in mouse brains upon treatment with 1,2-DCE, and in rat astrocytes exposed to 2-CE. In the present study, we analyzed the association of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) with MMP-9 overexpression in astrocytes treated with 2-CE. MMP-9, p65, c-Jun, and c-Fos were significantly upregulated by 2-CE treatment, which also enhanced phosphorylation of c-Jun, c-Fos and inhibitor of κBα (IκBα), and nuclear translocation of p65. Furthermore, inhibition of IκBα phosphorylation and AP-1 activity with the specific inhibitors could attenuate MMP-9 overexpression in the cells. On the other hand, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway suppressed the activation of both NF-κB and AP-1 in 2-CE-treated astrocytes. In conclusion, MMP-9 overexpression induced by 2-CE in astrocytes could be mediated at least in part through the p38 signaling pathway via activation of both NF-κB and AP-1. This study might provide novel clues for clarifying the mechanisms underlying 1,2-DCE associated cerebral edema. MDPI 2018-08-07 /pmc/articles/PMC6115792/ /pubmed/30087244 http://dx.doi.org/10.3390/cells7080096 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Tong
Jin, Xiaoxia
Liao, Yingjun
Sun, Qi
Luo, Chaohong
Wang, Gaoyang
Zhao, Fenghong
Jin, Yaping
Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes
title Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes
title_full Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes
title_fullStr Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes
title_full_unstemmed Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes
title_short Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes
title_sort association of nf-κb and ap-1 with mmp-9 overexpression in 2-chloroethanol exposed rat astrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115792/
https://www.ncbi.nlm.nih.gov/pubmed/30087244
http://dx.doi.org/10.3390/cells7080096
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