2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury.
2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury.
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DOI：
10.1016/j.taap.2012.11.009
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发表时间：
2013-01-15
影响因子：
3.8
通讯作者：
Ganey, Patricia E.
中科院分区：
文献类型：
--
作者：
Fullerton, Aaron M.;Roth, Robert A.;Ganey, Patricia E.
炎症在免疫介导的肝损伤中起主要作用，暴露于环境污染物，如2,3,7,8 -四氯二苯并-对二恶英（TCDD）已被报道改变炎症反应并影响免疫细胞活性。在这项研究中，我们验证了TCDD预处理会加重魔豆蛋白a （Con a）诱导的免疫介导肝损伤小鼠模型的肝毒性。小鼠在第0天用30µg/kg TCDD或对照剂预处理，然后在第4天静脉注射Con A或生理盐水。TCDD治疗小鼠未发生肝损伤；然而，tcdd预处理增加了中等剂量Con A （4-10 mg/kg）造成的肝损伤。TCDD预处理小鼠血浆中炎性细胞因子浓度发生改变，包括干扰素γ (IFNγ)， TCDD/Con - a诱导的IFNγ敲除小鼠的肝毒性减弱。在治疗后的不同时间，分离肝内免疫细胞，测定细胞活化标志物和细胞溶解蛋白的表达。TCDD预处理增加了Con A给药后活化的自然杀伤T细胞（NKT）比例和表达Fas配体（FasL）的细胞比例。此外，FasL基因敲除小鼠和CD18抗血清处理小鼠均可免受TCDD/Con - a诱导的肝毒性，这表明在TCDD/Con - a治疗肝损伤的发展过程中，效应免疫细胞和实质细胞靶点之间需要直接的细胞-细胞相互作用。综上所述，TCDD暴露增加了NKT细胞的激活，并通过IFNγ和FasL表达的机制加重了Con A诱导的免疫介导的肝损伤。
Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30µg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD-pretreatment increased liver injury resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell-cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression.
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DOI：
10.1084/jem.179.5.1529
发表时间：
1994-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mizuhara H;O'Neill E;Seki N;Ogawa T;Kusunoki C;Otsuka K;Satoh S;Niwa M;Senoh H;Fujiwara H
通讯作者：
Fujiwara H
影响因子：
15.3
作者：
Kaneko, Y;Harada, M;Kawano, T;Yamashita, M;Shibata, Y;Gejyo, F;Nakayama, T;Taniguchi, M
通讯作者：
Taniguchi, M
DOI：
10.1080/026520300283351
发表时间：
2000-04-01
影响因子：
2.9
作者：
Birnbaum, LS;Tuomisto, J
通讯作者：
Tuomisto, J
影响因子：
3.8
作者：
DILIBERTO, JJ;AKUBUE, PI;BIRNBAUM, LS
通讯作者：
BIRNBAUM, LS
影响因子：
13.5
作者：
Louis, H;LeMoine, O;Deviere, J
通讯作者：
Deviere, J