刀豆蛋白A
肝损伤
基因剔除小鼠
CD8型
细胞毒性T细胞
趋化因子
免疫学
T细胞
肿瘤坏死因子α
肝炎
免疫系统
生物
化学
内分泌学
内科学
医学
体外
受体
生物化学
作者
Weifeng Ge,Yan Gao,Yang Zhao,Yuxuan Yang,Qi Sun,Xiao Yang,Xi Xu,Jianfa Zhang
标识
DOI:10.1016/j.intimp.2020.106604
摘要
Concanavalin A (Con A) activates innate immunity and causes liver damage mediated by cytotoxic T lymphocytes (CTL) in mice. The Pancreatic lipase-related protein 2 (PLRP2) is induced by interleukin (IL)-4 in vitro in CTLs and associated with CTL functions. We examined the role of PLRP2 in a mouse model of Con A-induced T cell-mediated hepatitis. PLRP2-knockout and wild-type (WT) mice were inoculated with 20 mg/kg Con A. Mice lacking PLRP2 reduced Con A-induced hepatitis, which was manifested by a decrease in serum aminotransferase and histopathological assessment. The expression and secretion of cytokines including tumor necrosis factor-alpha (TNF-α), interferon (IFN)-γ, IL-6, and IL-1β were suppressed in Con A-treated PLRP2-knockout mice. In PLRP2 knockout mice, Con A-induced liver chemokines and adhesion molecules (such as MIP-1α, MIP-1β, ICAM-1 and MCP-1) were also down regulated. In the WT liver treated with Con A, the number of T cells (CD4+ and CD8+) and macrophages (CD11b+ F4/80+) increased significantly, while the lack of PLRP2 reduced the number of T cells in the liver, but had no effect on macrophages. The shift of the metabolic profiles was impaired in Con A-treated PLRP2-knockout mice compared to WT mice. In conclusion, these results indicate that PLRP2 deficiency reduces T-cell mediated Con A-induced hepatitis, and suggest PLRP2 is a potential target of anti-inflammatory and immunomodulatory drugs to treat immune-mediated hepatitis.
科研通智能强力驱动
Strongly Powered by AbleSci AI