Abstract：
:Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the induction of corticosteroid (CS) insensitivity. Chronic ozone exposure leads to a model of COPD with lung inflammation and emphysema. Mitogen-activated protein kinase phosphatase-1 (MKP-1) may underlie CS insensitivity in COPD. We determined the role played by MKP-1 by studying the effect of corticosteroids in wild-type C57/BL6J and MKP-1(-/-) mice after chronic ozone exposure. Mice were exposed to ozone (3 ppm, 3 h) 12 times over 6 weeks. Dexamethasone (0.1 or 2 mg/kg; intraperitoneally) was administered before each exposure. Mice were studied 24 h after final exposure. In ozone-exposed C57/BL6J mice, bronchial hyperresponsiveness (BHR) was not inhibited by both doses of dexamethasone, but in MKP-1(-/-) mice, there was a small inhibition by high dose dexamethasone (2 mg/kg). There was an increase in mean linear intercept after chronic ozone exposure in both strains which was CS-insensitive. There was lesser inflammation after low dose of dexamethasone in MKP-1(-/-) mice compared to C57/Bl6J mice. Epithelial and collagen areas were modulated in ozone-exposed MKP-1(-/-) mice treated with dexamethasone compared to C57/Bl6J mice. MKP-1 regulated the expression of MMP-12, IL-13 and KC induced by ozone but did not alter dexamethasone׳s effects. Bronchial hyperresponsiveness, lung inflammation and emphySEMa after chronic exposure are CS-insensitive, and the contribution of MKP-1 to CS sensitivity in this model was negligible.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Pinart M,Hussain F,Shirali S,Li F,Zhu J,Clark AR,Ammit AJ,Chung KFdoi
10.1016/j.ejphar.2014.10.003subject
Has Abstractpub_date
2014-12-05 00:00:00pages
108-14eissn
0014-2999issn
1879-0712pii
S0014-2999(14)00708-0journal_volume
744pub_type
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90312-t
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journal_title：European journal of pharmacology
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abstract：:This paper examines the biochemical and behaviour changes induced by an acute stress (five 10-s, 1-mA foot-shocks) in three groups of rats: (1) never stressed, (2) subjected to chronic variate stress for 20 days, (3) subjected to the same chronic stress and treated with 5 mg/kg per day amitriptyline. After 15 min, acu...
journal_title：European journal of pharmacology
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