title: [Mechanism of p38 mitogen-activated protein kinase inhibitor SB203580 to glucocorticoid sensitivity].
abstract: OBJECTIVE
  To establish a model of cigarette smoke exposure to asthmatic rats and glucocorticoid resistance induced by nicotine in alveolar epithelioid cells A549 and study the mechanism for the change of glucocorticoid sensitivity induced by p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580.
  
  
  METHODS
  Sixty Wistar rats were randomly divided into 4 groups: normal group, asthmatic group, cigarette smoke exposure to asthmatic group and SB203580 group. The mRNA expressions of glucocorticoid receptor (GR), heat shock protein 90 (HSP90) and p38 MAPK were detected by real time-polymerase chain reaction (RT-PCR) while their protein expressions detected by Western blot in vivo. A549 cells were divided averagely into 4 groups: group A: normal; group B: 1 µmol/L dexamethasone (DEX); group C: 1 µmol/L DEX +1 µmol/L nicotine; group D: 1 µmol/L DEX +1 µmol/L nicotine+1 µmol/L SB203580. Immunofluorescence staining was used to study the in vitro colocalization of glucocorticoid receptor (GR) in A549 cells.
  
  
  RESULTS
  The mRNA expression of GR was 0.671 ± 0.002 in cigarette smoke exposure to asthmatic group and 0.595 ± 0.061 in SB203580 group (P = 0.065). The protein expression of GR was 0.700 ± 0.033 in cigarette smoke exposure to asthmatic group and 0.628 ± 0.091 in SB203580 group (P = 0.148). The mRNA expression of HSP90 was 0.558 ± 0.009 in cigarette smoke exposure to asthmatic group and 0.377 ± 0.046 in SB203580 group (P = 0.000). The protein expression of HSP90 was 0.507 ± 0.030 in cigarette smoke exposure to asthmatic group and 0.402 ± 0.050 in SB203580 group (P = 0.005). The mRNA expression of p38 MAPK was 0.971 ± 0.012 in cigarette smoke exposure to asthmatic group and 0.278 ± 0.049 in SB203580 group (P = 0.000). The protein expression of p38 MAPK was 0.982 ± 0.038 in cigarette smoke exposure to asthmatic group and 0.338 ± 0.042 in SB203580 group (P = 0.000). The ratio of GR amount within A549 nucleus versus that in cytoplasm was 0.077 ± 0.047 in group C and 0.592 ± 0.249 in group D (P = 0.000).
  
  
  CONCLUSIONS
  The mechanism of SB203580 enhancing the corticosteroid sensitivity may be improving nuclear translocation of GR to elevate corticosteroid sensitivity.
authors.affiliation: Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Jiang-tao
authors.initials: JT
authors.lastname: Lin
authors.forename: Li-chao
authors.initials: LC
authors.lastname: Sun
authors.forename: Tong-liang
authors.initials: TL
authors.lastname: Zhou
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Shu
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D045744:Cell Line, Tumor; D005938:Glucocorticoids / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000378:metabolism; D008297:Male; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction; D012906:Smoke / Q000009:adverse effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D018841:HSP90 Heat-Shock Proteins; D007093:Imidazoles; D011725:Pyridines; D011965:Receptors, Glucocorticoid; D012906:Smoke; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580