Anne M van der Does1, Marieke Heijink2, Oleg A Mayboroda2, Louise J Persson3, Marianne Aanerud3, Per Bakke4, Tomas M Eagan5, Pieter S Hiemstra6, Martin Giera2. 1. Dept. of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: a.van_der_does@lumc.nl. 2. Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands. 3. Dept. of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway. 4. Dept. of Clinical Science, University of Bergen, Bergen, Norway. 5. Dept. of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway; Dept. of Clinical Science, University of Bergen, Bergen, Norway. 6. Dept. of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
Abstract
INTRODUCTION: Disturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be converted into lipid mediators here collectively named oxylipins. These include classical eicosanoids, but also pro-resolving mediators. A balanced production of pro-inflammatory and pro-resolving oxylipins is of importance for adequate inflammatory responses and subsequent return to homeostasis. OBJECTIVES: Here we investigated if PUFA metabolism is disturbed in COPD patients. METHODS: Free PUFA and oxylipin levels were measured in induced sputum samples from the Bergen COPD cohort and COPD exacerbation study using liquid chromatography-mass spectrometry. Additionally, effects of whole cigarette smoke on PUFA metabolism in air-liquid interface cultures of primary bronchial epithelial cells were assessed. RESULTS: Significantly lower levels of free alpha-linolenic acid, linoleic acid and eicosapentaenoic acid (EPA) were detected in sputum from stable COPD patients compared to controls. During acute exacerbation (AE), levels of free arachidonic acid and docosapentaenoic acid were higher than in stable COPD patients. Furthermore, levels of omega-3 EPA- and docosahexaenoic acid-derived oxylipins were lower in sputum from stable COPD patients compared to controls. Cyclooxygenase-2-converted mediators were mostly increased during AE. In vitro studies additionally showed that cigarette smoke exposure may also directly contribute to altered epithelial PUFA metabolism, and indirectly by causing airway epithelial remodelling. CONCLUSIONS: Our findings show significant differences in PUFA metabolism in COPD patients compared to controls, further changed during AE. Airway epithelial remodelling may contribute to these changes. These findings provide new insight in impaired inflammatory resolution in COPD.
INTRODUCTION: Disturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be converted into lipid mediators here collectively named oxylipins. These include classical eicosanoids, but also pro-resolving mediators. A balanced production of pro-inflammatory and pro-resolving oxylipins is of importance for adequate inflammatory responses and subsequent return to homeostasis. OBJECTIVES: Here we investigated if PUFA metabolism is disturbed in COPDpatients. METHODS: Free PUFA and oxylipin levels were measured in induced sputum samples from the Bergen COPD cohort and COPD exacerbation study using liquid chromatography-mass spectrometry. Additionally, effects of whole cigarette smoke on PUFA metabolism in air-liquid interface cultures of primary bronchial epithelial cells were assessed. RESULTS: Significantly lower levels of free alpha-linolenic acid, linoleic acid and eicosapentaenoic acid (EPA) were detected in sputum from stable COPDpatients compared to controls. During acute exacerbation (AE), levels of free arachidonic acid and docosapentaenoic acid were higher than in stable COPDpatients. Furthermore, levels of omega-3 EPA- and docosahexaenoic acid-derived oxylipins were lower in sputum from stable COPDpatients compared to controls. Cyclooxygenase-2-converted mediators were mostly increased during AE. In vitro studies additionally showed that cigarette smoke exposure may also directly contribute to altered epithelial PUFA metabolism, and indirectly by causing airway epithelial remodelling. CONCLUSIONS: Our findings show significant differences in PUFA metabolism in COPDpatients compared to controls, further changed during AE. Airway epithelial remodelling may contribute to these changes. These findings provide new insight in impaired inflammatory resolution in COPD.
Authors: Mahyar Aghapour; Alexander H V Remels; Simon D Pouwels; Dunja Bruder; Pieter S Hiemstra; Suzanne M Cloonan; Irene H Heijink Journal: Am J Physiol Lung Cell Mol Physiol Date: 2019-11-06 Impact factor: 5.464
Authors: Alla Y Molchanova; Svetlana N Rjabceva; Tigran B Melik-Kasumov; Nikolay B Pestov; Plamena R Angelova; Vadim V Shmanai; Olga L Sharko; Andrei V Bekish; Genevieve James; Hui Gyu Park; Irina A Udalova; J Thomas Brenna; Mikhail S Shchepinov Journal: Antioxidants (Basel) Date: 2022-03-31
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