title: [Effects of hypoxia on the expression of glucocorticoid receptor and the anti-inflammatory action of dexamethasone in human alveolar epithelial cells].
abstract: OBJECTIVE
  To study the changes in the expression levels of two isoforms of glucocorticoid receptor (GRα and GRβ) and the anti-inflammatory effect of dexamethasone in human alveolar epithelial cell under hypoxic conditions.
  
  
  METHODS
  Human alveolar epithelial cell line A549 was used as the model. Cells were cultured under normoxic (37°C, 950 mL/L air, 50 mL/L CO(2);) or hypoxic (37°C, 950 mL/L N(2);, 250 mL/L CO(2);) conditions for 24, 48 and 72 h, respectively. The expression levels of GRα and GRβ proteins in the cells were determined by Western blotting. Lipopolysaccharide (LPS, 10 μg/mL) and the different concentrations of dexamethasone (DEX, 10(-8);-10(-6); mol/L) were added together into the culture medium under normoxic or hypoxic conditions. 48 h later, radioimmunoassay (RIA) was used to measure the level of IL-8 in the culture supernatants.
  
  
  RESULTS
  The GRα protein level of the normoxia group was not significantly different from that of the hypoxia group at 24 h time point (P>0.05). But at the 48 h and 72 h time points, the GRα protein level of the hypoxia groups was lower than that of the corresponding normoxia groups (P<0.05, P<0.01, respectively). The GRα protein levels decreased progressively in the hypoxia groups (P<0.05), while the levels were not significantly different among the corresponding normoxia groups (P>0.05); The GRβ protein levels of the 24, 48, and 72 h hypoxia groups were not different from those in the corresponding normoxia groups (P>0.05). At 48 h after 10(-7); or 10(-6); mol/L DEX was added, IL-8 levels in the culture supernatants of the hypoxia groups were higher than those in the corresponding normoxia groups (P<0.05).
  
  
  CONCLUSIONS
  Hypoxia can down-regulate the GRα protein level in a time-dependent manner in A549 cells and impair the anti-inflammatory effect of DEX.
authors.affiliation: Department of Respiratory Medicine, Hospital of Anhui Provinical Corps, Chinese People's Armed Police Forces, Hefei 230041, China. huangyan0416@126.com
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Na
authors.initials: N
authors.lastname: Ni
authors.forename: Congzhe
authors.initials: C
authors.lastname: Lu
authors.forename: Yunyou
authors.initials: Y
authors.lastname: Duan
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015687:Cell Hypoxia; D002460:Cell Line; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D003907:Dexamethasone