title: Inhibition of monoamine oxidase-B by selegiline reduces cigarette smoke-induced oxidative stress and inflammation in airway epithelial cells.
abstract: Chronic obstructive pulmonary disease (COPD) is caused by the build-up of oxidative stress-induced damages due to cigarette smoking, but how monoamine oxidase (MAO)-B signaling is involved remains unclear. This study aims to establish the involvement of MAO-B signaling pathways in cigarette smoke medium (CSM)-induced oxidative stress and inflammation in human airway epithelial cells (AECs). CSM treatment increased MAO-B activity, ROS levels and IL-8 release in AECs. Pretreatment with MAO-B selective inhibitor selegiline reversed the CSM-induced changes in MAO-B activity, ROS levels and IL-8 release in a dose-dependent manner. Selegiline also reversed CSM-induced changes of anti-oxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activities, GSH/GSSG ratio, as well expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). The effects of selegiline are partially driven through the nuclear factor erythroid 2 related factor 2 (Nrf2) and cytosol translocation of its negative regulator, BTB and CNC homolog 1 (Bach1). Nevertheless, selegiline fully reversed the CSM-induced effects on IKK, cytoplasmic IκB expression, and nuclear translocation of nuclear factor-κB (NF-κB) p65 subunit. Our study demonstrated that in AECs, inhibition of MAO-B using selegiline reversed the CSM-induced oxidative stress and inflammation. These data may provide a novel strategy for therapy in COPD.
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong; Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong.
authors.forename: Kenneth W K
authors.initials: KW
authors.lastname: Liu
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong; Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong.
authors.forename: Mary S M
authors.initials: MS
authors.lastname: Ip
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong; Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong; Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong. Electronic address: judithmak@hku.hk.
authors.forename: Judith C W
authors.initials: JC
authors.lastname: Mak
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002460:Cell Line; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011014:Pneumonia / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D017382:Reactive Oxygen Species / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C508606:CXCL8 protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8; D008996:Monoamine Oxidase Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012906:Smoke; D012642:Selegiline; D008995:Monoamine Oxidase
keywords: Airway epithelium; Cigarette smoke medium; Inflammation; Monoamine oxidase; Oxidative stress; Selegiline