Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells

Azithromycin is a member of macrolides, utilized in the treatment of infections. Independently, these antibiotics also possess anti-inflammatory and immunomodulatory properties. Phospholipase Ay 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 A(2), (sPLA(2)) and (cPLA(2)), respectively, which are induced by an inflammatory trigger. In this respect we studied the lipopolysaccharide (LPS)-mediated production or secretion of sPLA(2) and cPLA(2) 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 sPLA(2)-IIA levels in A549 cells. This inhibition was rather due to reduced PLA(2)G2A mRNA expression and secretion of sPLA(2)-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 5PLA(2)-IIA from alveolar macrophages. The levels of LPS-induced c-PLA(2) 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 5PIA(2)-IIA, while it does not affect alveolar macrophages. (C) 2015 Elsevier B.V. All rights reserved.