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Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1

BACKGROUND: Molecular mechanisms involved in the oxidative stress induced glucocorticoids insensitivity remain elusive. The mitogen-activated protein kinase phosphatase (MKP) 1 mediates a part of glucocorticoids action and can be modified by exogenous oxidants. Whether oxidant ozone (O(3)) can affec...

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Autores principales: Bao, Aihua, Li, Feng, Zhang, Min, Chen, Yuqing, Zhang, Pengyu, Zhou, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196074/
https://www.ncbi.nlm.nih.gov/pubmed/25287866
http://dx.doi.org/10.1186/s12931-014-0126-x
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author Bao, Aihua
Li, Feng
Zhang, Min
Chen, Yuqing
Zhang, Pengyu
Zhou, Xin
author_facet Bao, Aihua
Li, Feng
Zhang, Min
Chen, Yuqing
Zhang, Pengyu
Zhou, Xin
author_sort Bao, Aihua
collection PubMed
description BACKGROUND: Molecular mechanisms involved in the oxidative stress induced glucocorticoids insensitivity remain elusive. The mitogen-activated protein kinase phosphatase (MKP) 1 mediates a part of glucocorticoids action and can be modified by exogenous oxidants. Whether oxidant ozone (O(3)) can affect the function of MKP-1 and hence blunt the response to corticotherapy is not clear. METHODS: Here we employed a murine model of asthma established with ovalbumin (OVA) sensitization and challenge to evaluate the influence of O(3) on the inhibitory effect of dexamethasone on AHR and airway inflammation, and by administration of SB239063, a selective p38 MAPK inhibitor, to explore the underlying involvements of the activation of p38 MAPK and the expression of MKP-1. RESULTS: Ozone exposure not only aggravated the pulmonary inflammation and AHR, but also decreased the inhibitory effects of dexamethasone, accompanied by the elevated oxidative stress, airway neutrophilia, enhanced phosphorylation of p38 MAPK, and upregulated expression of IL-17. Administration of SB239063 caused significant inhibition of the p38 MAPK phosphorylation, alleviation of the airway neutrophilia, and decrement of the ozone-induced IL-17 expression, and partly restored the ozone-impaired effects of dexamethasone. Ozone exposure not only decreased the protein expression of MKP-1, but also diminished the dexamethasone-mediated induction process of MKP-1 mRNA and protein expression. CONCLUSIONS: The glucocorticoids insensitivity elicited by ozone exposure on current asthma model may involve the enhanced phosphorylation of p38 MAPK and disturbed expression of MKP-1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-014-0126-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-41960742014-10-15 Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1 Bao, Aihua Li, Feng Zhang, Min Chen, Yuqing Zhang, Pengyu Zhou, Xin Respir Res Research BACKGROUND: Molecular mechanisms involved in the oxidative stress induced glucocorticoids insensitivity remain elusive. The mitogen-activated protein kinase phosphatase (MKP) 1 mediates a part of glucocorticoids action and can be modified by exogenous oxidants. Whether oxidant ozone (O(3)) can affect the function of MKP-1 and hence blunt the response to corticotherapy is not clear. METHODS: Here we employed a murine model of asthma established with ovalbumin (OVA) sensitization and challenge to evaluate the influence of O(3) on the inhibitory effect of dexamethasone on AHR and airway inflammation, and by administration of SB239063, a selective p38 MAPK inhibitor, to explore the underlying involvements of the activation of p38 MAPK and the expression of MKP-1. RESULTS: Ozone exposure not only aggravated the pulmonary inflammation and AHR, but also decreased the inhibitory effects of dexamethasone, accompanied by the elevated oxidative stress, airway neutrophilia, enhanced phosphorylation of p38 MAPK, and upregulated expression of IL-17. Administration of SB239063 caused significant inhibition of the p38 MAPK phosphorylation, alleviation of the airway neutrophilia, and decrement of the ozone-induced IL-17 expression, and partly restored the ozone-impaired effects of dexamethasone. Ozone exposure not only decreased the protein expression of MKP-1, but also diminished the dexamethasone-mediated induction process of MKP-1 mRNA and protein expression. CONCLUSIONS: The glucocorticoids insensitivity elicited by ozone exposure on current asthma model may involve the enhanced phosphorylation of p38 MAPK and disturbed expression of MKP-1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-014-0126-x) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-08 2014 /pmc/articles/PMC4196074/ /pubmed/25287866 http://dx.doi.org/10.1186/s12931-014-0126-x Text en © Bao et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bao, Aihua
Li, Feng
Zhang, Min
Chen, Yuqing
Zhang, Pengyu
Zhou, Xin
Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1
title Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1
title_full Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1
title_fullStr Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1
title_full_unstemmed Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1
title_short Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1
title_sort impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 mapk and mkp-1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196074/
https://www.ncbi.nlm.nih.gov/pubmed/25287866
http://dx.doi.org/10.1186/s12931-014-0126-x
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