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
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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