Impact of azithromycin treatment on Macrophage gene expression in subjects with cystic fibrosis

Background: Azithromycin treatment improves clinical parameters in patients with CF, and alters macrophage activation from a pro-inflammatory (M1) phenotype to a pro-fibrotic, alternatively activated (M2) phenotype. The transcriptional profile of cells from patients receiving azithromycin is unknown. Methods: Gene expression in association with macrophage polarization, inflammation, and tissue remodeling was assessed from sputum samples collected from patients with CF. Transcriptional profiles and clinical characteristics, including azithromycin therapy, were compared. Results: Expression of NOS2 and TNF alpha was decreased in subjects receiving azithromycin, whereas expression of M2-associated genes was unaffected. Principal component analysis revealed gene expression profiles consistent with Ml- (MMP9, NOS2, and TLR4) or M2-polarization (CCL18, fibronectin, and MR1) in select subject groups. These expression signatures did not significantly correlate with clinical characteristics. Conclusions: Pro-inflammatory gene expression was low in subjects receiving AZM. Genes were stratified into groupings characteristic of Ml- or M2-polarization, suggesting that overall polarization status is distinct among patient groups. (C) 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.