title: Impact of azithromycin treatment on macrophage gene expression in subjects with cystic fibrosis.
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.
authors.affiliation: Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone, Lexington, KY 40536, United States; Department of Pharmacy Practice, University of Nebraska College of Pharmacy, 986000 Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Cory
authors.affiliation: Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone, Lexington, KY 40536, United States; Department of Medicine, University of Alabama at Birmingham, 1918 University Blvd., Birmingham, AL 35294, United States.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Birket
authors.affiliation: Department of Internal Medicine, University of Kentucky College of Medicine, 138 Leader Avenue, Lexington, KY 40506, United States.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Murphy
authors.affiliation: Section of Pulmonary Medicine, Department of Pediatrics, The Ohio State University, Nationwide Children's Hospital, 700 Children's Dr., Columbus, OH 43205, United States.
authors.forename: Don
authors.initials: D
authors.lastname: Hayes
authors.affiliation: Department of Pediatrics, University of Kentucky, 138 Leader Avenue, Lexington, KY 40506, United States.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Anstead
authors.affiliation: Department of Pediatrics, University of Kentucky, 138 Leader Avenue, Lexington, KY 40506, United States.
authors.forename: Jamshed F
authors.initials: JF
authors.lastname: Kanga
authors.affiliation: Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone, Lexington, KY 40536, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kuhn
authors.affiliation: Department of Biostatistics, University of Kentucky College of Medicine, 725 Rose Street, Lexington, KY 40536, United States.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Bush
authors.affiliation: Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone, Lexington, KY 40536, United States. Electronic address: david.feola@uky.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Feola
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D017963:Azithromycin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology; D008297:Male; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism; D012129:Respiratory Function Tests
chemical_list: D000900:Anti-Bacterial Agents; D018836:Inflammation Mediators; D011971:Receptors, Immunologic; D017963:Azithromycin
keywords: Azithromycin; Cystic fibrosis; Macrophage phenotype
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