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

Theodore J. Cory, Susan E. Birket, Brian S. Murphy, Don Hayes, Michael I. Anstead, Jamshed F. Kanga, Robert J. Kuhn, Heather M. Bush, David J. Feola

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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 TNFα was decreased in subjects receiving azithromycin, whereas expression of M2-associated genes was unaffected. Principal component analysis revealed gene expression profiles consistent with M1- (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 M1- or M2-polarization, suggesting that overall polarization status is distinct among patient groups.

Original languageEnglish
Pages (from-to)164-171
Number of pages8
JournalJournal of Cystic Fibrosis
Volume13
Issue number2
DOIs
StatePublished - Mar 2014

Keywords

  • Azithromycin
  • Cystic fibrosis
  • Macrophage phenotype

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

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