Arsenic trioxide alleviates airway hyperresponsiveness and promotes apoptosis of CD4+ T lymphocytes: evidence for involvement of the ER stress-CHOP pathway

作者:Li, K.; Zhang, L.; Xiang, X.; Gong, S.; Ma, L.; Xu, L.; Wang, G.; Liu, Y.; Ji, X.; Liu, S.; Chen, P.; Zeng, H.; Li, J.*
来源:Irish Journal of Medical Science, 2013, 182(4): 573-583.
DOI:10.1007/s11845-013-0928-8

摘要

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. @@@ We wanted to research the effect of arsenic trioxide on asthma. @@@ 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. @@@ 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 mu M, 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 @@@ 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.