Allergy and Airway: Asthma III |

Oxidative Stress Impairs Glucocorticoids Sensitivity of Allergic Asthma Animal Model FREE TO VIEW

Aihua Bao, PhD; Xin Zhou, MD
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Shanghai Jiao Tong University, Shanghai First People's Hospital, Shanghai, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A32. doi:10.1016/j.chest.2016.02.034
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: To observe the influence of ozone inhalation on the typical therapeutic effects of glucocorticoids and further to explore the involvements of p38MAPK activation and MKP-1 expression upon a mouse asthma model.

METHODS: Mice were sensitized and challenged with ovalbumin (OVA), dexamethasone were administrated ip 1 hr before each challenge (day24,25,26). Ozone expsoure (1.0 ppm 2hr) were performed on day 23, 25 and 27, and SB239063 were injected 1hr before and 4hr after each exposure. Enhanced pause (Penh) were measured at day 28 and followed by bronchoalveolar lavage (BAL). Lung tissues were collected for analysis of expression of inflammatory genes, MKP-1 and p38MAPK.

RESULTS: Ozone inhalation significantly increased the AHR and airway inflammation of OVA model. Dexamethasone significantly decreased the AHR and airway inflammation of mice from OVA model. These inhibitory effects were significantly decreased after the ozone exposure. Administration of SB239063 partly restored the impaired effects of dexamethasone, parallel with inhibitions of the AHR and airway inflammation, especially the lung expression of IL-17 mRNA, in mice of O3-exposed OVA model. The activation of p38MAPK was promoted by ozone inhalation and inhibited by SB239063. There was no striking effect of dexamethasone on activation of p38MAPK except in O3-exposed OVA model group. Dexamethasone increased the mRNA and protein expression of MKP-1 on lungs of mice only from OVA group. This effects were diminished by ozone inhalation regardless of SB239063 administration. O3 inhalation promoted the expression of MKP-1 on mRNA but not on protein level.

CONCLUSIONS: Ozone inhalation disturbs the inhibitory effects of glucocorticoids on allergic airway inflammation. This disturbance may involve the activation of p38 MAPK, induction of Th17 cytokines and negative regulation on MKP-1 protein expression.

CLINICAL IMPLICATIONS: Glucocorticoid resistance is a common and hard-to-treat problem in chronic severe asthmatic patients. This study explored the underlying involvements of p38 MAPK and MKP-1 in the oxidative stress induced steroids resistance in a mouse asthma model, which may contribute to the knowledge accumulation to help understand the underlying mechanisms of Glucocorticoid resistance.

DISCLOSURE: The following authors have nothing to disclose: Aihua Bao, Xin Zhou

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