Involvements of p38 MAPK and oxidative stress in the ozone-induced enhancement of AHR and pulmonary inflammation in an allergic asthma model

Respiratory Research

Research

Aihua Bao¹  Feng Li¹  Min Zhang¹  Hong Yang¹  Xin Zhou¹  Wuping Bao¹  Yuqin Chen¹  Qiang Li¹  Suqin Ben¹  Jie Ji² 

[1] Department of Respiratory Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, 200080, Shanghai, People’s Republic of China;Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, PO Box 210, -17177, Stockholm, SE, Sweden;

关键词: Asthma exacerbation;    Ozone;    p38 MAPK;    Oxidative stress;    α-tocopherol;   

DOI  :  10.1186/s12931-017-0697-4

 received in 2017-07-21, accepted in 2017-12-11,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundExposure to ambient ozone (O3) increases the susceptivity to allergens and triggers exacerbations in patients with asthma. However, the detailed mechanisms of action for O3 to trigger asthma exacerbations are still unclear.MethodsAn ovalbumin (OVA)-established asthmatic mouse model was selected to expose to filtered air (OVA-model) or 1.0 ppm O3 (OVA-O3 model) during the process of OVA challenge. Next, the possible involvements of p38 MAPK and oxidative stress in the ozone actions on the asthma exacerbations were investigated on the mice of OVA-O3 model by treating them with SB239063 (a p38 MAPK inhibitor), and/or the α-tocopherol (antioxidant). Biological measurements were conducted including airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL), inflammation in the airway lumen and lung parenchyma, the phosphorylation of p38 MAPK and heat shock protein (HSP) 27 in the tracheal tissues, and the malondialdehyde (MDA) content and the glutathione peroxidase (GSH-Px) activity in lung tissues.ResultsIn OVA-allergic mice, O3 exposure deteriorated airway hyperresponsiveness (AHR), airway resistance (Raw), lung compliance (CL) and pulmonary inflammation, accompanied by the increased oxidative stress in lung tissues and promoted p38 MAPK and HSP27 phosphorylation in tracheal tissues. Administration of SB239063 (a p38 MAPK inhibitor) on OVA-O3 model exclusively mitigated the Raw, the CL, and the BAL IL-13 content, while α-tocopherol (antioxidant) differentially reduced the BAL number of eosinophils and macrophages, the content of BAL hyaluronan, the peribronchial inflammation, as well as the mRNA expression of TNF-α and IL-5 in the lung tissues of OVA-O3 model. Administration of these two chemical inhibitors similarly inhibited the AHR, the BAL IFN-γ and IL-6 production, the perivascular lung inflammation and the lung IL-17 mRNA expression of OVA-O3 model. Interestingly, the combined treatment of both compounds together synergistically inhibited neutrophil counts in the BALF and CXCL-1 gene expression in the lung.ConclusionsO3 exposure during the OVA challenge process promoted exacerbation in asthma. Both p38 MAPK and oxidative stress were found to play a critical role in this process and simultaneous inhibition of these two pathways significantly reduced the O3-elicited detrimental effects on the asthma exacerbation.

【 授权许可】

CC BY   
© The Author(s). 2018