title: Mycobacterium tuberculosisESAT6 and CPF10 Induce Adenosine Deaminase 2 mRNA Expression in Monocyte-Derived Macrophages.
abstract: BACKGROUND
  Delayed hypersensitivity plays a large role in the pathogenesis of tuberculous pleural effusion (TPE). Macrophages infected with liveMycobacterium tuberculosis(MTB) increase the levels of adenosine deaminase2 (ADA2) in the pleural fluid of TPE patients. However, it is as yet unclear whether ADA2 can be produced by macrophages when challenged with MTB antigens alone. This study therefore evaluated the levels of ADA2 mRNA expression, using monocyte-derived macrophages (MDMs) stimulated with MTB antigens.
  
  
  METHODS
  Purified monocytes from the peripheral blood mononuclear cells of healthy volunteers were differentiated into macrophages using granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF). The MDMs were stimulated with early secretory antigenic target protein 6 (ESAT6) and culture filtrate protein 10 (CFP10). The mRNA expression levels for the cat eye syndrome chromosome region, candidate 1 (CECR1) gene encoding ADA2 were then measured.
  
  
  RESULTS
  CECR1 mRNA expression levels were significantly higher in MDMs stimulated with ESAT6 and CFP10, than in the unstimulated MDMs. When stimulated with ESAT6, M-CSF-treated MDMs showed more pronounced CECR1 mRNA expression than GM-CSF-treated MDMs. Interferon-γ decreased the ESAT6- and CFP10-induced CECR1 mRNA expression in MDMs. CECR1 mRNA expression levels were positively correlated with mRNA expression of tumor necrosis factor α and interleukin 10, respectively.
  
  
  CONCLUSIONS
  ADA2 mRNA expression increased when MDMs were stimulated with MTB antigens alone. This partly indicates that pleural fluid ADA levels could increase in patients with culture-negative TPE. Our results may be helpful in improving the understanding of TPE pathogenesis.
authors.affiliation: Department of Physiology, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Tumor Heterogeneity and Network (THEN) Research Center, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Bae
authors.affiliation: Department of Physiology, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Tumor Heterogeneity and Network (THEN) Research Center, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Suyeon
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Physiology, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Tumor Heterogeneity and Network (THEN) Research Center, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Ha-Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Seung Ick
authors.initials: SI
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jaehee
authors.initials: J
authors.lastname: Lee
keywords: Adenosine; Cat Eye Syndrome Chromosome Region, Candidate 1 Protein, Human; Macrophage; Mycobacterium tuberculosis Antigen