Exposure 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.
An 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.
In 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.
O3 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.
Health effects of outdoor air pollution. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. Am J Respir Crit Care Med. 1996;153(1):3–50. CrossRef
Wiegman CH, Li F, Clarke CJ, Jazrawi E, Kirkham P, Barnes PJ, Adcock IM, Chung KF. A comprehensive analysis of oxidative stress in the ozone-induced lung inflammation mouse model. Clin Sci (Lond). 2014;126(6):425–40. CrossRef
Vagaggini B, Bartoli ML, Cianchetti S, Costa F, Bacci E, Dente FL, Di Franco A, Malagrino L, Paggiaro P. Increase in markers of airway inflammation after ozone exposure can be observed also in stable treated asthmatics with minimal functional response to ozone. Respir Res. 2010;11:5. CrossRefPubMedPubMedCentral
Pichavant M, Goya S, Meyer EH, Johnston RA, Kim HY, Matangkasombut P, Zhu M, Iwakura Y, Savage PB, DeKruyff RH, et al. Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. J Exp Med. 2008;205(2):385–93. CrossRefPubMedPubMedCentral
Mabalirajan U, Aich J, Leishangthem GD, Sharma SK, Dinda AK, Ghosh B. Effects of vitamin E on mitochondrial dysfunction and asthma features in an experimental allergic murine model. J Appl Physiol (1985). 2009;107(4):1285–92. CrossRef
Bao A, Liang L, Li F, Zhang M, Zhou X. Effects of acute ozone exposure on lung peak allergic inflammation of mice. Front Biosci (Landmark Ed). 2013;18:838–51. CrossRef
Larsen JK, Yamboliev IA, Weber LA, Gerthoffer WT. Phosphorylation of the 27-kDa heat shock protein via p38 MAP kinase and MAPKAP kinase in smooth muscle. Am J Phys. 1997;273(5 Pt 1):L930–40.
Williams AS, Leung SY, Nath P, Khorasani NM, Bhavsar P, Issa R, Mitchell JA, Adcock IM, Chung KF. Role of TLR2, TLR4, and MyD88 in murine ozone-induced airway hyperresponsiveness and neutrophilia. J Appl Physiol (1985). 2007;103(4):1189–95. CrossRef
- Involvements of p38 MAPK and oxidative stress in the ozone-induced enhancement of AHR and pulmonary inflammation in an allergic asthma model
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II