Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression
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 i...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-03-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | http://www.mdpi.com/1422-0067/20/5/1078 |
id |
doaj-3c8706e3c6674185b9791a6ab195816d |
---|---|
record_format |
Article |
spelling |
doaj-3c8706e3c6674185b9791a6ab195816d2020-11-24T23:56:13ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-03-01205107810.3390/ijms20051078ijms20051078Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 ExpressionPei-Sung Hsu0Chia-Mo Lin1Jia-Feng Chang2Chi-Sheng Wu3Kee-Chin Sia4I-Ta Lee5Kuo-Yang Huang6Wei-Ning Lin7Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, TaiwanDivision of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, TaiwanDepartment of Internal Medicine, En-Chu-Kong Hospital, New Taipei City 237, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung 407, TaiwanGraduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242, TaiwanObesity 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.http://www.mdpi.com/1422-0067/20/5/1078leptincPLA2αCOX-2ROSc-Juninflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pei-Sung Hsu Chia-Mo Lin Jia-Feng Chang Chi-Sheng Wu Kee-Chin Sia I-Ta Lee Kuo-Yang Huang Wei-Ning Lin |
spellingShingle |
Pei-Sung Hsu Chia-Mo Lin Jia-Feng Chang Chi-Sheng Wu Kee-Chin Sia I-Ta Lee Kuo-Yang Huang Wei-Ning Lin Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression International Journal of Molecular Sciences leptin cPLA2α COX-2 ROS c-Jun inflammation |
author_facet |
Pei-Sung Hsu Chia-Mo Lin Jia-Feng Chang Chi-Sheng Wu Kee-Chin Sia I-Ta Lee Kuo-Yang Huang Wei-Ning Lin |
author_sort |
Pei-Sung Hsu |
title |
Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression |
title_short |
Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression |
title_full |
Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression |
title_fullStr |
Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression |
title_full_unstemmed |
Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression |
title_sort |
participation of nadph oxidase-related reactive oxygen species in leptin-promoted pulmonary inflammation: regulation of cpla2α and cox-2 expression |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-03-01 |
description |
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. |
topic |
leptin cPLA2α COX-2 ROS c-Jun inflammation |
url |
http://www.mdpi.com/1422-0067/20/5/1078 |
work_keys_str_mv |
AT peisunghsu participationofnadphoxidaserelatedreactiveoxygenspeciesinleptinpromotedpulmonaryinflammationregulationofcpla2aandcox2expression AT chiamolin participationofnadphoxidaserelatedreactiveoxygenspeciesinleptinpromotedpulmonaryinflammationregulationofcpla2aandcox2expression AT jiafengchang participationofnadphoxidaserelatedreactiveoxygenspeciesinleptinpromotedpulmonaryinflammationregulationofcpla2aandcox2expression AT chishengwu participationofnadphoxidaserelatedreactiveoxygenspeciesinleptinpromotedpulmonaryinflammationregulationofcpla2aandcox2expression AT keechinsia participationofnadphoxidaserelatedreactiveoxygenspeciesinleptinpromotedpulmonaryinflammationregulationofcpla2aandcox2expression AT italee participationofnadphoxidaserelatedreactiveoxygenspeciesinleptinpromotedpulmonaryinflammationregulationofcpla2aandcox2expression AT kuoyanghuang participationofnadphoxidaserelatedreactiveoxygenspeciesinleptinpromotedpulmonaryinflammationregulationofcpla2aandcox2expression AT weininglin participationofnadphoxidaserelatedreactiveoxygenspeciesinleptinpromotedpulmonaryinflammationregulationofcpla2aandcox2expression |
_version_ |
1725459041792032768 |