title: Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells.
abstract: Azithromycin is a member of macrolides, utilized in the treatment of infections. Independently, these antibiotics also possess anti-inflammatory and immunomodulatory properties. Phospholipase A2 isotypes, which are implicated in the pathophysiology of inflammatory lung disorders, are produced by alveolar macrophages and other lung cells during inflammatory response and can promote lung injury by destructing lung surfactant. The aim of the study was to investigate whether in lung cells azithromycin can inhibit secretory and cytosolic phospholipases A2, (sPLA2) and (cPLA2), respectively, which are induced by an inflammatory trigger. In this respect, we studied the lipopolysaccharide (LPS)-mediated production or secretion of sPLA2 and cPLA2 from A549 cells, a cancer bronchial epithelial cell line, and alveolar macrophages, isolated from bronchoalveolar lavage fluid of ARDS and control patients without cardiopulmonary disease or sepsis. Pre-treatment of cells with azithromycin caused a dose-dependent decrease in the LPS-induced sPLA2-IIA levels in A549 cells. This inhibition was rather due to reduced PLA2G2A mRNA expression and secretion of sPLA2-IIA protein levels, as observed by western blotting and indirect immunofluorescence by confocal microscopy, respectively, than to the inhibition of the enzymic activity per se. On the contrary, azithromycin had no effect on the LPS-induced production or secretion of sPLA2-IIA from alveolar macrophages. The levels of LPS-induced c-PLA2 were not significantly affected by azithromycin in either cell type. We conclude that azithromycin exerts anti-inflammatory properties on lung epithelial cells through the inhibition of both the expression and secretion of LPS-induced sPLA2-IIA, while it does not affect alveolar macrophages.
authors: Laboratory of Biochemistry, Chemistry Department, School of Science, University of Ioannina, Greece.
authors: Eirini
authors: E
authors: Kitsiouli
authors: Laboratory of Biochemistry, Chemistry Department, School of Science, University of Ioannina, Greece.
authors: Georgia
authors: G
authors: Antoniou
authors: Laboratory of Biochemistry, Chemistry Department, School of Science, University of Ioannina, Greece.
authors: Helen
authors: H
authors: Gotzou
authors: Laboratory of Biochemistry, Chemistry Department, School of Science, University of Ioannina, Greece.
authors: Michalis
authors: M
authors: Karagiannopoulos
authors: Institute of Molecular Biology and Biotechnology, Biomedical Research, Foundation for Research and Technology, Ioannina, Greece; Laboratory of Biological Chemistry, Medical School, University of Ioannina, Greece.
authors: Dimitris
authors: D
authors: Basagiannis
authors: Institute of Molecular Biology and Biotechnology, Biomedical Research, Foundation for Research and Technology, Ioannina, Greece; Laboratory of Biological Chemistry, Medical School, University of Ioannina, Greece.
authors: Savvas
authors: S
authors: Christoforidis
authors: Department of Intensive Care Medicine, School of Medicine, University of Ioannina, Greece. Electronic address: gnakos@cc.uoi.gr.
authors: George
authors: G
authors: Nakos
authors: Laboratory of Biochemistry, Chemistry Department, School of Science, University of Ioannina, Greece. Electronic address: mlekka@cc.uoi.gr.
authors: Marilena E
authors: ME
authors: Lekka
mesh_terms: D017963:Azithromycin / Q000494:pharmacology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009928:Organ Specificity; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D017963:Azithromycin; D054467:Phospholipases A2
keywords: A549 cells; ARDS; Alveolar macrophages; Azithromycin; Lung epithelial cells; Phospholipase A(2)