Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression
Autor: | Kuo-Yang Huang, Wei-Ning Lin, Chia-Mo Lin, Chi-Sheng Wu, Pei-Sung Hsu, Kee-Chin Sia, Jia-Feng Chang, I-Ta Lee |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine lcsh:Chemistry Mice chemistry.chemical_compound 0302 clinical medicine Pulmonary fibrosis cPLA2α Lung lcsh:QH301-705.5 Spectroscopy Mice Inbred ICR NADPH oxidase biology Leptin digestive oral and skin physiology ROS General Medicine Computer Science Applications 030220 oncology & carcinogenesis Receptors Leptin medicine.symptom medicine.medical_specialty Adipokine Inflammation Lung injury leptin Article Catalysis Inorganic Chemistry 03 medical and health sciences Cell Line Tumor Internal medicine medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology Leptin receptor business.industry Group IV Phospholipases A2 Organic Chemistry c-Jun NADPH Oxidases Pneumonia COX-2 medicine.disease Oxidative Stress 030104 developmental biology Endocrinology lcsh:Biology (General) lcsh:QD1-999 chemistry Cyclooxygenase 2 inflammation Apocynin biology.protein Reactive Oxygen Species business |
Zdroj: | International Journal of Molecular Sciences Volume 20 Issue 5 International Journal of Molecular Sciences, Vol 20, Iss 5, p 1078 (2019) |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms20051078 |
Popis: | Obesity is a worldwide epidemic problem and correlates to varieties of acute or chronic lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. An increase of leptin, a kind of adipokine, in lean mice plasma has been found to impair immune responses and facilitate the infection of Klebsiella pneumoniae, resulting in increased pneumonia severity. Also, a higher leptin level is found in exhaled breath condensates of obese or asthmatic subjects, compared to healthy ones, suggesting that leptin is involved in the occurrence or exacerbation of lung injury. In previous studies, we showed that leptin stimulated cytosolic phospholipase A2-&alpha (cPLA2&alpha ) gene expression in lung alveolar type II cells via mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-&kappa B)-activated coactivator p300. Herein, we show that the in vivo application of leptin in the respiratory system upregulated the expression of inflammatory proteins cPLA2&alpha and cyclooxygenase-2 (COX-2) together with leukocyte infiltration. Treatment with an ROS scavenger (N-acetylcysteine, NAC), an NADPH oxidase inhibitor (apocynin), or an activating protein (AP)-1 inhibitor (tanshinone IIA) attenuated leptin-mediated cPLA2&alpha /COX-2 expression and leukocyte recruitment in the lung. Leptin increased intracellular oxidative stress in a leptin receptor (OB-R) and NADPH oxidase-dependent manner, leading to the phosphorylation of the AP-1 subunit c-Jun. In summation, leptin increased lung cPLA2&alpha /COX-2 expression and leukocyte recruitment via the NADPH oxidase/ROS/AP-1 pathway. Understanding the inflammatory effects of leptin on the pulmonary system provides opportunities to develop strategies against lung injury related to metabolic syndrome or obesity. |
Databáze: | OpenAIRE |
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