title: Pro-phagocytic Effects of Thymoquinone on Cigarette Smoke-exposed Macrophages Occur by Modulation of the Sphingosine-1-phosphate Signalling System.
abstract: Oxidative stress, inflammation, increased bronchial epithelial cell apoptosis, and deficient phagocytic clearance of these cells (efferocytosis) by the alveolar macrophages are present in chronic obstructive pulmonary disease (COPD) and in response to cigarette smoke. We previously showed that the macrophage dysfunction is associated with changes to the sphingosine-1-phosphate (S1P) signalling system. We hypothesized that the antioxidant/anti-inflammatory agent, thymoquinone, would improve macrophage phagocytosis via modulation of the S1P system and protect bronchial epithelial cells from cigarette smoke or lipopolysaccharide (LPS)-induced apoptosis. Phagocytosis was assessed using flow cytometry, S1P mediators by Real-Time PCR, and apoptosis of 16HBE bronchial epithelial cells using flow cytometry and immunohistochemistry. Cigarette smoke and LPS decreased phagocytosis and increased S1P receptor (S1PR)-5 mRNA in THP-1 macrophages. Thymoquinone enhanced efferocytic/phagocytic ability, antagonized the effects of cigarette smoke extract and LPS on phagocytosis and S1PR5, and protected bronchial epithelial cells from cigarette smoke-induced apoptosis. Thymoquinone is worth further investigating as a potential therapeutic strategy for smoking-related lung diseases.
authors.affiliation: a Lung Research, Hanson Institute , Adelaide , South Australia.|b Department of Medicine , University of Adelaide , South Adelaide , South Australia.|c Department of Medical Laboratory Technology , University of Tabuk , Saudi Arabia.
authors.forename: Jameel
authors.initials: J
authors.lastname: Barnawi
authors.affiliation: a Lung Research, Hanson Institute , Adelaide , South Australia.
authors.forename: Hai B
authors.initials: HB
authors.lastname: Tran
authors.affiliation: a Lung Research, Hanson Institute , Adelaide , South Australia.
authors.forename: Eugene
authors.initials: E
authors.lastname: Roscioli
authors.affiliation: a Lung Research, Hanson Institute , Adelaide , South Australia.|b Department of Medicine , University of Adelaide , South Adelaide , South Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Hodge
authors.affiliation: a Lung Research, Hanson Institute , Adelaide , South Australia.|b Department of Medicine , University of Adelaide , South Adelaide , South Australia.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Jersmann
authors.affiliation: d Centre for Neuroscience Anatomy & Histology, Flinders University , Adelaide , South Australia , Australia.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haberberger
authors.affiliation: a Lung Research, Hanson Institute , Adelaide , South Australia.|b Department of Medicine , University of Adelaide , South Adelaide , South Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodge
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D045424:Complex Mixtures / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D062789:Tobacco Products
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D045424:Complex Mixtures; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; D012906:Smoke; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C003466:thymoquinone
keywords: Chronic obstructive pulmonary disease; cigarette smoke; macrophage; sphingosine-1 phosphate; thymoquinone