title: Arsenic trioxide alleviates airway hyperresponsiveness and promotes apoptosis of CD4+ T lymphocytes: evidence for involvement of the ER stress-CHOP pathway.
abstract: BACKGROUND
  Asthma is a chronic inflammatory disorder of the airway. Arsenic trioxide (ATO) is an ancient Chinese medicine, which is used to treat psoriasis, asthma, and acute promyelocytic leukemia.
  
  
  OBJECTIVE
  We wanted to research the effect of arsenic trioxide on asthma.
  
  
  METHODS
  Using a murine model of asthma, the airway hyperresponsiveness was conducted by the Buxco pulmonary function apparatus. Total cell counts of BALF were counted with a counting chamber. Histopathological analysis of lung tissues was conducted by hematoxylin-eosin or periodic acid-schiff stain. CD4+T cells were purified from the spleen by positive selection, using immunomagnetic beads. Apoptosis measurements were done with Annexin-V/PI staining. Western blot analysis and real time-PCR were performed to assess the expression of C/EBP-homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), respectively. RNA interference was conducted to inhibit the expression of CHOP.
  
  
  RESULTS
  We found that arsenic trioxide treatment alleviated airway hyperresponsiveness and reduced inflammation of the lung in asthmatic mice. Furthermore, arsenic trioxide treatment promoted apoptosis of CD4+T cells in vivo and in vitro. When CD4+T cells were cultured with arsenic trioxide for 5 h at a concentration of 5 μM, the expression of GRP78 and CHOP was increased. Treatment of CD4+T cells with CHOP siRNA, provided partial resistance to arsenic trioxide-induced apoptosis of CD4+T cells
  
  
  CONCLUSIONS
  These data demonstrated that arsenic trioxide can reduce the severity of asthma attacks and induce the apoptosis of CD4+ T cell which the ER stress-CHOP pathway involved.
authors.affiliation: Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Xiang
authors.forename: S
authors.initials: S
authors.lastname: Gong
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Ji
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Zeng
authors.forename: J
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010087:Oxides / Q000494:pharmacology*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D001152:Arsenicals; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D010087:Oxides; D051742:Transcription Factor CHOP; D000077237:Arsenic Trioxide