Interleukin 6 and hepatocyte regeneration in acetaminophen toxicity in the mouse
Interleukin 6 and hepatocyte regeneration in acetaminophen toxicity in the mouse
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DOI：
10.1016/j.bbrc.2003.08.085
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发表时间：
2003-10-03
影响因子：
3.1
通讯作者：
Hinson, JA
中科院分区：
文献类型：
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作者：
James, LP;Lamps, LW;Hinson, JA
为了确定IL-6在对乙酰氨基酚（APAP）毒性中的重要性，将野生型（WT）和IL-6敲除（KO）小鼠用APAP（300 mg/kg i. p.）并在4和24 h处死。血清AST水平和组织病理学检查两组间无差异。此外，APAP蛋白结合和硝基酪氨酸形成的相对量相等。随后，将WT和KO小鼠用APAP（300 mg/kg i. p.）并在24、48和72 h处死。WT小鼠中AST在48小时恢复正常，但KO小鼠中直到72小时才恢复正常。两组小鼠的组织病理学变化的严重程度相当;然而，KO小鼠中存在较少的再生肝细胞。增殖细胞核抗原（PCNA）的免疫组织化学显示KO小鼠的染色减少。用IL-6预处理KO小鼠降低了IL-6 KO小鼠中的AST和正常化的PCNA染色。这些数据表明，IL-6在小鼠中APAP毒性后的肝细胞再生中是重要的。(C)2003年爱思唯尔公司All rights reserved.
To determine the importance of IL-6 in acetaminophen (APAP) toxicity, wild type (WT) and IL-6 knock out (KO) mice were dosed with APAP (300 mg/kg i.p.) and sacrificed at 4 and 24 h. No differences were found between the two groups by analysis of serum AST levels or histopathology. Also, the relative amounts of APAP protein binding and nitrotyrosine formation were equal. Subsequently, WT and KO mice were dosed with APAP (300 mg/kg i.p.) and sacrificed at 24, 48, and 72 h. AST normalized by 48 h in the WT mice, but not until 72h in the KO mice. The severity of the histopathological alterations was comparable in the two groups of mice; however, fewer regenerating hepatocytes were present in the KO mice. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) showed reduced staining in the KO mice. Pretreatment of KO mice with IL-6 lowered AST and normalized PCNA staining in the IL-6 KO mice. These data suggest that IL-6 is important in hepatocyte regeneration following APAP toxicity in the mouse. (C) 2003 Elsevier Inc. All rights reserved.