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

被引:32
作者
Cory, Theodore J. [1 ,2 ]
Birket, Susan E. [1 ,3 ]
Murphy, Brian S. [4 ]
Hayes, Don, Jr. [5 ]
Anstead, Michael I. [6 ]
Kanga, Jamshed F. [6 ]
Kuhn, Robert J. [1 ]
Bush, Heather M. [7 ]
Feola, David J. [1 ]
机构
[1] Univ Kentucky, Coll Pharm, Dept Pharm Practice & Sci, Lexington, KY 40536 USA
[2] Univ Nebraska, Coll Pharm, Dept Pharm Practice, Omaha, NE 68198 USA
[3] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[4] Univ Kentucky, Coll Med, Dept Internal Med, Lexington, KY 40506 USA
[5] Ohio State Univ, Nationwide Childrens Hosp, Dept Pediat, Sect Pulm Med, Columbus, OH 43205 USA
[6] Univ Kentucky, Dept Pediat, Lexington, KY 40506 USA
[7] Univ Kentucky, Coll Med, Dept Biostat, Lexington, KY 40536 USA
关键词
Macrophage phenotype; Cystic fibrosis; Azithromycin; PSEUDOMONAS-AERUGINOSA; PULMONARY-FIBROSIS; CHILDREN;
D O I
10.1016/j.jcf.2013.08.007
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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.
引用
收藏
页码:164 / 171
页数:8
相关论文
共 30 条
  • [1] Azithromycin increases in vitro fibronectin production through interactions between macrophages and fibroblasts stimulated with Pseudomonas aeruginosa
    Cory, Theodore J.
    Birket, Susan E.
    Murphy, Brian S.
    Mattingly, Cynthia
    Breslow-Deckman, Jessica M.
    Feola, David J.
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2013, 68 (04) : 840 - 851
  • [2] The phenotype of murine wound macrophages
    Daley, Jean M.
    Brancato, Samielle K.
    Thomay, Alan A.
    Reichner, Jonathan S.
    Albina, Jorge E.
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 2010, 87 (01) : 59 - 67
  • [3] Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial
    Equi, A
    Balfour-Lynn, IM
    Bush, A
    Rosenthal, M
    [J]. LANCET, 2002, 360 (9338) : 978 - 984
  • [4] Azithromycin Alters Macrophage Phenotype and Pulmonary Compartmentalization during Lung Infection with Pseudomonas
    Feola, David J.
    Garvy, Beth A.
    Cory, Theodore J.
    Birket, Susan E.
    Hoy, Heather
    Hayes, Don, Jr.
    Murphy, Brian S.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2010, 54 (06) : 2437 - 2447
  • [5] Matrix metalloprotease-9 dysregulation in lower airway secretions of cystic fibrosis patients
    Gaggar, Amit
    Li, Yao
    Weathington, Nathaniel
    Winkler, Margaret
    Kong, Michele
    Jackson, Patricia
    Blalock, J. E.
    Clancy, J. P.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2007, 293 (01) : L96 - L104
  • [6] Pathophysiology and management of pulmonary infections in cystic fibrosis
    Gibson, RL
    Burns, JL
    Ramsey, BW
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 168 (08) : 918 - 951
  • [7] Plasma TGF-β1 in Pediatric Cystic Fibrosis: Potential Biomarker of Lung Disease and Response to Therapy
    Harris, William T.
    Muhlebach, Marianne S.
    Oster, Robert A.
    Knowles, Michael R.
    Clancy, J. P.
    Noah, Terry L.
    [J]. PEDIATRIC PULMONOLOGY, 2011, 46 (07) : 688 - 695
  • [8] Pulmonary TH2 response in Pseudomonas aeruginos-infected patients with cystic fibrosis
    Hartl, D
    Griese, M
    Kappler, M
    Zissel, G
    Reinhardt, D
    Rebhan, C
    Schendel, DJ
    Krauss-Etschmann, S
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2006, 117 (01) : 204 - 211
  • [9] Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis
    Hauser, Alan R.
    Jain, Manu
    Bar-Meir, Maskit
    McColley, Susanna A.
    [J]. CLINICAL MICROBIOLOGY REVIEWS, 2011, 24 (01) : 29 - 70
  • [10] Latent-TGF-β:: An overview
    Lawrence, DA
    [J]. MOLECULAR AND CELLULAR BIOCHEMISTRY, 2001, 219 (1-2) : 163 - 170