title: Human leukocyte antigen-G expression in differentiated human airway epithelial cells: lack of modulation by Th2-associated cytokines.
abstract: BACKGROUND
  Human leukocyte antigen (HLA)-G is a nonclassical class I antigen with immunomodulatory roles including up-regulation of suppressor T regulatory lymphocytes. HLA-G was recently identified as an asthma susceptibility gene, and expression of a soluble isoform, HLA-G5, has been demonstrated in human airway epithelium. Increased presence of HLA-G5 has been demonstrated in bronchoalveolar lavage fluid recovered from patients with mild asthma; this suggests a role for this isoform in modulating airway inflammation though the mechanisms by which this occurs is unclear. Airway inflammation associated with Th2 cytokines such as IL-4 and IL-13 is a principal feature of asthma, but whether these cytokines elicit expression of HLA-G is not known.
  
  
  METHODS
  We examined gene and protein expression of both soluble (G5) and membrane-bound (G1) HLA-G isoforms in primary differentiated human airway epithelial cells collected from normal lungs and grown in air-liquid interface culture. Cells were treated with up to 10 ng/ml of either IL-4, IL-5, or IL-13, or 100 ng/ml of the immunomodulatory cytokine IL-10, or 10,000 U/ml of the Th1-associated cytokine interferon-beta, for 24 hr, after which RNA was isolated for evaluation by quantitative PCR and protein was collected for Western blot analysis.
  
  
  RESULTS
  HLA-G5 but not G1 was present in dAEC as demonstrated by quantitative PCR, western blot and confocal microscopy. Neither G5 nor G1 expression was increased by the Th2-associated cytokines IL-4, IL-5 or IL-13 over 24 hr, nor after treatment with IL-10, but was increased 4.5 ± 1.4 fold after treatment with 10,000 U/ml interferon-beta.
  
  
  CONCLUSIONS
  These data demonstrate the constitutive expression of a T lymphocyte regulatory molecule in differentiated human airway epithelial cells that is not modulated by Th2-associated cytokines.
authors: University of Chicago, Section of Pulmonary and Critical Care Medicine, Chicago, IL 60637, USA. swhite@medicine.bsd.uchicago.edu
authors: Steven R
authors: SR
authors: White
authors: Dagan A
authors: DA
authors: Loisel
authors: Randi
authors: R
authors: Stern
authors: Bharathi
authors: B
authors: Laxman
authors: Timothy
authors: T
authors: Floreth
authors: Bertha A
authors: BA
authors: Marroquin
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology*; D059951:HLA-G Antigens / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000276:immunology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D059951:HLA-G Antigens