Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression

Pei Sung Hsu, Chia Mo Lin, Jia Feng Chang, Chi Sheng Wu, Kee Chin Sia, I. Ta Lee, Kuo Yang Huang, Wei Ning Lin

研究成果: 雜誌貢獻文章同行評審

11 引文 斯高帕斯(Scopus)

摘要

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-α (cPLA2α) gene expression in lung alveolar type II cells via mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB)-activated coactivator p300. Herein, we show that the in vivo application of leptin in the respiratory system upregulated the expression of inflammatory proteins cPLA2α 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 cPLA2α/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 cPLA2α/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.
原文英語
文章編號1078
頁(從 - 到)1078
期刊International Journal of Molecular Sciences
20
發行號5
DOIs
出版狀態已發佈 - 3月 1 2019
對外發佈

ASJC Scopus subject areas

  • 催化
  • 分子生物學
  • 光譜
  • 電腦科學應用
  • 物理與理論化學
  • 有機化學
  • 無機化學

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