naa a22 4500 51074110X CHVBK 20180411083028.0 cr unu---uuuuu 180411e20131201xx s 000 0 eng 10.1007/s11845-013-0928-8 doi (NATIONALLICENCE)springer-10.1007/s11845-013-0928-8 Arsenic trioxide alleviates airway hyperresponsiveness and promotes apoptosis of CD4+ T lymphocytes: evidence for involvement of the ER stress-CHOP pathway [Elektronische Daten] [K. Li, L. Zhang, X. Xiang, S. Gong, L. Ma, L. Xu, G. Wang, Y. Liu, X. Ji, S. Liu, P. Chen, H. Zeng, J. Li] 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 5h at a concentration of 5μM, 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. Royal Academy of Medicine in Ireland, 2013 Arsenic trioxide nationallicence Asthma nationallicence CD4+ T cells nationallicence Apoptosis nationallicence CHOP nationallicence Li K. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Zhang L. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Xiang X. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Gong S. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Ma L. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Xu L. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Wang G. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Liu Y. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Ji X. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Liu S. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Chen P. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Zeng H. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Li J. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut Irish Journal of Medical Science Springer London 182/4(2013-12-01), 573-583 0021-1265 182:4<573 2013 182 11845 https://doi.org/10.1007/s11845-013-0928-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11845-013-0928-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li K. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Zhang L. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Xiang X. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Gong S. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Ma L. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Xu L. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Wang G. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Liu Y. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Ji X. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Liu S. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Chen P. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Zeng H. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 700 1- Li J. Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China aut NATIONALLICENCE 773 0- Irish Journal of Medical Science Springer London 182/4(2013-12-01), 573-583 0021-1265 182:4<573 2013 182 11845 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer