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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6115792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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