Tobacco smoking aggravates airway inflammation by upregulating endothelin-2 and activating the c-Jun amino terminal kinase pathway in asthma

Autor: Jiechen Zhu, Maoqing Guo, Yanan Liu, Shu-yang Zhu, Bi Chen, Fangfang Han, Xiao Han
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Immunology
Rats
Sprague-Dawley
Leukocyte Count
03 medical and health sciences
0302 clinical medicine
Malondialdehyde
Internal medicine
Tobacco Smoking
medicine
Animals
Immunology and Allergy
Lung
Dexamethasone
Endothelin-2
Inflammation
Pharmacology
chemistry.chemical_classification
medicine.diagnostic_test
biology
business.industry
Glutathione peroxidase
JNK Mitogen-Activated Protein Kinases
Interleukin
respiratory system
Glutathione
Asthma
Bosentan
Up-Regulation
respiratory tract diseases
Ovalbumin
030104 developmental biology
Bronchoalveolar lavage
Endocrinology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
biology.protein
Cytokines
Endothelin receptor
business
Bronchoalveolar Lavage Fluid
Signal Transduction
medicine.drug
Zdroj: International Immunopharmacology. 77:105916
ISSN: 1567-5769
DOI: 10.1016/j.intimp.2019.105916
Popis: Background Asthma is closely associated with tobacco smoking (TS) and is more difficult to effectively treat after exposure to TS. Objective To observe the effects of TS on the expression of endothelin-2 (ET-2) and airway inflammation in asthmatic rats and to explore the related mechanisms. Methods We established an animal model of asthma with ovalbumin (OVA)/Al(OH)3 and subjected different animal groups to TS and/or dexamethasone/bosentan. The differences in the inflammatory cell infiltration, the pathological changes to the bronchial wall and the bronchial smooth muscle thickness, and the expression of ET-2, c-Jun amino terminal kinase (JNK1/2), malondialdehyde (MDA), and glutathione peroxidase (GSH) in the lung tissue and of interleukin (IL)-7 in bronchoalveolar lavage fluid (BALF) were assessed. Results Exposure to TS or OVA caused an obvious increase in the inflammatory cells in the BALF over what was observed in the control group. In asthma models, the expression of ET-1, JNK1/2, MDA, and GSH in the lung tissues, as well as that of IL-17 in the BALF, was increased. After treatment with dexamethasone/bosentan, the expression of IL-17, JNK1/2, MDA, and GSH decreased compared to the smoking group; airway inflammation and the staining intensity in the lung tissue were also reduced. Conclusion TS exposure can clearly exacerbate airway inflammation in asthmatic rats, while bosentan can alleviate airway inflammation through regulation of the ET-2/JNK1/2 signalling pathway.
Databáze: OpenAIRE
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