title: A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression.
abstract: BACKGROUND
  "Phosphatase and tensin homolog deleted on chromosome 10" (PTEN) is mostly considered to be a cancer-related gene, and has been suggested to be a new pathway of pathogenesis of asthma. The purpose of this study was to investigate the effects of the glucocorticoid, dexamethasone, on PTEN regulation.
  
  
  METHODS
  OVA-challenged mice were used as an asthma model to investigate the effect of dexamethasone on PTEN regulation. Immunohistochemistry was used to detect expression levels of PTEN protein in lung tissues. The human A549 cell line was used to explore the possible mechanism of action of dexamethasone on human PTEN regulation in vitro. A luciferase reporter construct under the control of PTEN promoter was used to confirm transcriptional regulation in response to dexamethasone.
  
  
  RESULTS
  PTEN protein was found to be expressed at low levels in lung tissues in asthmatic mice; but the expression was restored after treatment with dexamethasone. In A549 cells, human PTEN was up-regulated by dexamethasone treatment. The promoter-reporter construct confirmed that dexamethasone could regulate human PTEN transcription. Treatment with the histone deacetylase inhibitor, TSA, could increase PTEN expression in A549 cells, while inhibition of histone acetylase (HAT) by anacardic acid attenuated dexamethasone-induced PTEN expression.
  
  
  CONCLUSIONS
  Based on the data a new mechanism is proposed where glucocorticoids treat asthma partly through up-regulation of PTEN expression. The in vitro studies also suggest that the PTEN pathway may be involved in human asthma.
authors.affiliation: Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, PR China.
authors.forename: ZhenHua
authors.initials: Z
authors.lastname: Ni
authors.forename: JiHong
authors.initials: J
authors.lastname: Tang
authors.forename: ZhuYing
authors.initials: Z
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: QingGe
authors.initials: Q
authors.lastname: Chen
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.forename: XiongBiao
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse