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Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway
Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone II...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938387/ https://www.ncbi.nlm.nih.gov/pubmed/29765317 http://dx.doi.org/10.3389/fphar.2018.00263 |
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author | Guan, Ruijuan Wang, Jian Li, Ziying Ding, Mingjing Li, Defu Xu, Guihua Wang, Tao Chen, Yuqin Yang, Qian Long, Zhen Cai, Zhou Zhang, Chenting Liang, Xue Dong, Lian Zhao, Li Zhang, Haiyun Sun, Dejun Lu, Wenju |
author_facet | Guan, Ruijuan Wang, Jian Li, Ziying Ding, Mingjing Li, Defu Xu, Guihua Wang, Tao Chen, Yuqin Yang, Qian Long, Zhen Cai, Zhou Zhang, Chenting Liang, Xue Dong, Lian Zhao, Li Zhang, Haiyun Sun, Dejun Lu, Wenju |
author_sort | Guan, Ruijuan |
collection | PubMed |
description | Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α–induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1β, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD. |
format | Online Article Text |
id | pubmed-5938387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59383872018-05-14 Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway Guan, Ruijuan Wang, Jian Li, Ziying Ding, Mingjing Li, Defu Xu, Guihua Wang, Tao Chen, Yuqin Yang, Qian Long, Zhen Cai, Zhou Zhang, Chenting Liang, Xue Dong, Lian Zhao, Li Zhang, Haiyun Sun, Dejun Lu, Wenju Front Pharmacol Pharmacology Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α–induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1β, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD. Frontiers Media S.A. 2018-05-01 /pmc/articles/PMC5938387/ /pubmed/29765317 http://dx.doi.org/10.3389/fphar.2018.00263 Text en Copyright © 2018 Guan, Wang, Li, Ding, Li, Xu, Wang, Chen, Yang, Long, Cai, Zhang, Liang, Dong, Zhao, Zhang, Sun and Lu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Guan, Ruijuan Wang, Jian Li, Ziying Ding, Mingjing Li, Defu Xu, Guihua Wang, Tao Chen, Yuqin Yang, Qian Long, Zhen Cai, Zhou Zhang, Chenting Liang, Xue Dong, Lian Zhao, Li Zhang, Haiyun Sun, Dejun Lu, Wenju Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway |
title | Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway |
title_full | Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway |
title_fullStr | Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway |
title_full_unstemmed | Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway |
title_short | Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway |
title_sort | sodium tanshinone iia sulfonate decreases cigarette smoke-induced inflammation and oxidative stress via blocking the activation of mapk/hif-1α signaling pathway |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938387/ https://www.ncbi.nlm.nih.gov/pubmed/29765317 http://dx.doi.org/10.3389/fphar.2018.00263 |
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