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Ectopic B7-H4-Ig expression attenuates concanavalin A-induced hepatic injury
Authors:Jun-Fa Xu,Huan Xiao,Guo-Yan Hu,Shu-Hua Zheng,Wei Liu,Chun-Lei Yuan,Heng Yang,Jing Lü  ,Fang Zheng,Cong-Yi Wang,Fei-Li Gong
Affiliation:1. Department of Clinical Immunology, Guangdong Medical College, Dongguan, Guangdong, 523808, People''s Republic of China;2. Research Institute of Laboratory Medicine, Guangdong Medical College, Dongguan, Guangdong, 523808, PR China;3. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China;4. Center for Biotechnology and Genomic Medicine, Department of Pathology, Medical College of Georgia, 1120 15th Street, CA4098, Augusta, GA 30912, USA
Abstract:Previous studies demonstrate that both membrane B7-H4 and B7-H4-Ig fusion protein could inhibit T-cell responses. In the present study, we explored the potential effect of B7-H4-Ig on liver injury in a hepatitis mouse model induced by concanavalin A (ConA). A B7-H4-Ig construct was introduced into animals by the hydrodynamic gene delivery approach. It was found that ectopic expression of B7-H4-Ig could inhibit ConA-induced elevation of serum levels of ALT and AST, suppress liver necrosis and even mortality of mice. Furthermore, we observed that pretreatment of B7-H4-Ig dramatically decreased serum levels and the expression of mRNA for IL-2, IFN-γ and IL-4, but increased IL-10 in ConA-treated mice. Our results suggest that B7-H4-Ig may protect animals from liver injury induced by ConA, which could be associated with reduced serum levels for IL-2, IFN-γ and IL-4 as well as enhanced IL-10 production.
Keywords:B7-H4   concanavalin A   hydrodynamics- based gene delivery   hepatic injury   IL-2   IFN-γ   IL-4   IL-10
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