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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.

Bao A, Li F, Zhang M, Chen Y, Zhang P, Zhou X - Respir. Res. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao tong University, 100 Haining Road, Shanghai 200080China. xzhou53@163.com.

ABSTRACT

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 (O3) 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 O3 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.

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Related in: MedlinePlus

SB239063 caused changes in oxidative stress and the phosphorylation of p38 MAPK and the expression of MKP-1 in lung tissues. Interpretation of A) to E) is same to those in Figure 3. *:p < 0.05; **:p < 0.01; ***: p < 0.001; n = 7.
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Fig5: SB239063 caused changes in oxidative stress and the phosphorylation of p38 MAPK and the expression of MKP-1 in lung tissues. Interpretation of A) to E) is same to those in Figure 3. *:p < 0.05; **:p < 0.01; ***: p < 0.001; n = 7.

Mentions: SB239063 affected neither the concentration of MDA nor the activity of GSH-Px in O3-exposed asthmatic mice (Figure 5A and B).Figure 5


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

Bao A, Li F, Zhang M, Chen Y, Zhang P, Zhou X - Respir. Res. (2014)

SB239063 caused changes in oxidative stress and the phosphorylation of p38 MAPK and the expression of MKP-1 in lung tissues. Interpretation of A) to E) is same to those in Figure 3. *:p < 0.05; **:p < 0.01; ***: p < 0.001; n = 7.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4196074&req=5

Fig5: SB239063 caused changes in oxidative stress and the phosphorylation of p38 MAPK and the expression of MKP-1 in lung tissues. Interpretation of A) to E) is same to those in Figure 3. *:p < 0.05; **:p < 0.01; ***: p < 0.001; n = 7.
Mentions: SB239063 affected neither the concentration of MDA nor the activity of GSH-Px in O3-exposed asthmatic mice (Figure 5A and B).Figure 5

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao tong University, 100 Haining Road, Shanghai 200080China. xzhou53@163.com.

ABSTRACT

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 (O3) 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 O3 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.

Show MeSH
Related in: MedlinePlus