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. AIM: 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.
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. AIM: 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: H Zinszner; M Kuroda; X Wang; N Batchvarova; R T Lightfoot; H Remotti; J L Stevens; D Ron Journal: Genes Dev Date: 1998-04-01 Impact factor: 11.361
Authors: Penny E Lovat; Serafina Oliverio; Marco Corazzari; Carlo Rodolfo; Marco Ranalli; Bojidar Goranov; Gerry Melino; Christopher P F Redfern; Mauro Piacentini Journal: Cancer Res Date: 2003-11-01 Impact factor: 12.701
Authors: Karin Engström; Tomasz K Wojdacz; Francesco Marabita; Philip Ewels; Max Käller; Francesco Vezzi; Nicola Prezza; Joel Gruselius; Marie Vahter; Karin Broberg Journal: Arch Toxicol Date: 2016-11-12 Impact factor: 5.153