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Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages
BACKGROUND: The objective of this study was to study the anti-inflammatory effect and possibly involved molecular mechanisms of matrine on oxidized low-density lipoprotein (ox-LDL)-exposed macrophages. MATERIAL/METHODS: Cultured human macrophages (THP-1 cell line) were exposed to ox-LDL at final con...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561390/ https://www.ncbi.nlm.nih.gov/pubmed/31156213 http://dx.doi.org/10.12659/MSM.917151 |
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author | Zhou, Junli Ma, Wangxia Wang, Xincheng Liu, Hongbo Miao, Youliang Wang, Juanli Du, Peng Chen, Yani Zhang, Yong Liu, Zhongwei |
author_facet | Zhou, Junli Ma, Wangxia Wang, Xincheng Liu, Hongbo Miao, Youliang Wang, Juanli Du, Peng Chen, Yani Zhang, Yong Liu, Zhongwei |
author_sort | Zhou, Junli |
collection | PubMed |
description | BACKGROUND: The objective of this study was to study the anti-inflammatory effect and possibly involved molecular mechanisms of matrine on oxidized low-density lipoprotein (ox-LDL)-exposed macrophages. MATERIAL/METHODS: Cultured human macrophages (THP-1 cell line) were exposed to ox-LDL at final concentrations of 0, 25, 50, and 100 μg/mL. Several cells were then treated with matrine at serial diluted concentrations. 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) staining was used to evaluate reactive oxygen species (ROS) production; a colorimetric method was used to determine the cellular antioxidant capacity; production of pro-inflammatory cytokines interleukin (IL)18 and tumor necrosis factor (TNF)α were determined by enzyme-linked immunosorbent assay (ELISA); and immunoblot assay was used to assess the relative protein phosphorylation and expression. RESULTS: ox-LDL exposure significantly elevated intracellular ROS level and supernatant IL18 and TNFα concentrations, but impaired total antioxidant capacity (TAC) of macrophages. The relative phosphorylations of MAPK kinase kinases (MKK)6, MKK3, and p38 mitogen-activated protein kinases (MAPK) were increased by ox-LDL exposure. The expression levels of IL18 and TNFα were also increased in ox-LDL-treated macrophages. The matrine treatment reduced intracellular ROS level and supernatant IL18 and TNFα concentrations and increased TAC in a concentration- dependent manner. The relative phosphorylations of MKK6, MKK3, and p38 MAPK were reduced after matrine administration. Moreover, the expression levels of IL18 and TNFα were also decreased by matrine treatment, in a concentration-dependent manner. CONCLUSIONS: ox-LDL increases inflammatory response in macrophages by activating the ROS-mediated MKKs/p38 MAPK-induced inflammatory signaling pathway. Matrine suppresses ox-LDL-induced inflammatory by inhibiting the MKKs/p38 MAPK signaling pathway. |
format | Online Article Text |
id | pubmed-6561390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65613902019-06-26 Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages Zhou, Junli Ma, Wangxia Wang, Xincheng Liu, Hongbo Miao, Youliang Wang, Juanli Du, Peng Chen, Yani Zhang, Yong Liu, Zhongwei Med Sci Monit Lab/In Vitro Research BACKGROUND: The objective of this study was to study the anti-inflammatory effect and possibly involved molecular mechanisms of matrine on oxidized low-density lipoprotein (ox-LDL)-exposed macrophages. MATERIAL/METHODS: Cultured human macrophages (THP-1 cell line) were exposed to ox-LDL at final concentrations of 0, 25, 50, and 100 μg/mL. Several cells were then treated with matrine at serial diluted concentrations. 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) staining was used to evaluate reactive oxygen species (ROS) production; a colorimetric method was used to determine the cellular antioxidant capacity; production of pro-inflammatory cytokines interleukin (IL)18 and tumor necrosis factor (TNF)α were determined by enzyme-linked immunosorbent assay (ELISA); and immunoblot assay was used to assess the relative protein phosphorylation and expression. RESULTS: ox-LDL exposure significantly elevated intracellular ROS level and supernatant IL18 and TNFα concentrations, but impaired total antioxidant capacity (TAC) of macrophages. The relative phosphorylations of MAPK kinase kinases (MKK)6, MKK3, and p38 mitogen-activated protein kinases (MAPK) were increased by ox-LDL exposure. The expression levels of IL18 and TNFα were also increased in ox-LDL-treated macrophages. The matrine treatment reduced intracellular ROS level and supernatant IL18 and TNFα concentrations and increased TAC in a concentration- dependent manner. The relative phosphorylations of MKK6, MKK3, and p38 MAPK were reduced after matrine administration. Moreover, the expression levels of IL18 and TNFα were also decreased by matrine treatment, in a concentration-dependent manner. CONCLUSIONS: ox-LDL increases inflammatory response in macrophages by activating the ROS-mediated MKKs/p38 MAPK-induced inflammatory signaling pathway. Matrine suppresses ox-LDL-induced inflammatory by inhibiting the MKKs/p38 MAPK signaling pathway. International Scientific Literature, Inc. 2019-06-03 /pmc/articles/PMC6561390/ /pubmed/31156213 http://dx.doi.org/10.12659/MSM.917151 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Lab/In Vitro Research Zhou, Junli Ma, Wangxia Wang, Xincheng Liu, Hongbo Miao, Youliang Wang, Juanli Du, Peng Chen, Yani Zhang, Yong Liu, Zhongwei Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages |
title | Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages |
title_full | Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages |
title_fullStr | Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages |
title_full_unstemmed | Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages |
title_short | Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages |
title_sort | matrine suppresses reactive oxygen species (ros)-mediated mkks/p38-induced inflammation in oxidized low-density lipoprotein (ox-ldl)-stimulated macrophages |
topic | Lab/In Vitro Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561390/ https://www.ncbi.nlm.nih.gov/pubmed/31156213 http://dx.doi.org/10.12659/MSM.917151 |
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