抗白细胞介素-18在小鼠模型中预防伴刀豆球蛋白A诱导的肝纤维化的机制。

The mechanism of how anti-IL-18 prevents concanavalin-A-induced hepatic fibrosis on a mouse model.

作者信息

Zhang Yewei, Li Ping, Li Guoqiang, Huang Xinli, Meng Qingyang, Lau Wan Y, Wang Xuehao

机构信息

The Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

出版信息

J Surg Res. 2007 Sep;142(1):175-83. doi: 10.1016/j.jss.2007.01.024. Epub 2007 Jun 7.

DOI:10.1016/j.jss.2007.01.024

PMID:17559879

Abstract

BACKGROUND

The administration of concanavalin A (ConA) induces severe hepatic fibrosis in mice. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) were the key cytokines involved in the process. The aim of this research was to explore the effects and the mechanisms of IL-18 and anti-IL-18 on hepatic fibrosis in a ConA induced hepatic fibrosis model in BABL-C mice.

MATERIALS AND METHODS

One hundred eighty BABL-C mice were randomly divided into five groups (Group a, b, c, d, e). The mice were administered saline, immunoglobulin G, ConA, IL-18 + ConA, Anti-IL-18 + ConA, respectively. At 1, 7, 14, 21 wk, the levels of serum alanine aminotransferase, TNF-alpha, IFN-gamma, IL-4, matrix metalloproteinase (MMP)-2-RNA, and tissue inhibitor of metalloproteinase-1-mRNA were measured.

RESULTS

The levels of serum TNF-alpha and IFN-gamma detected in the IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). Similarly, the levels of MMP-2-RNA and tissue inhibitor of metalloproteinase-1-mRNA expressed in IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). A majority of these cytokines was secreted by CD4(+)T cells.

CONCLUSIONS

The immunological response to hepatic fibrosis by repeated injection of ConA in the mouse model was aggravated by IL-18 and blocked by anti-IL-18.

摘要

背景

注射伴刀豆球蛋白A（ConA）可诱导小鼠发生严重肝纤维化。肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和白细胞介素4（IL-4）是该过程中的关键细胞因子。本研究旨在探讨白细胞介素18（IL-18）及抗IL-18对BABL-C小鼠ConA诱导的肝纤维化模型肝纤维化的影响及机制。

材料与方法

180只BABL-C小鼠随机分为五组（a组、b组、c组、d组、e组）。分别给予小鼠生理盐水、免疫球蛋白G、ConA、IL-18 + ConA、抗IL-18 + ConA。在第1、7、14、21周时，检测血清丙氨酸转氨酶、TNF-α、IFN-γ、IL-4、基质金属蛋白酶（MMP）-2-RNA和金属蛋白酶组织抑制剂-1-mRNA水平。

结果

IL-18 + ConA组检测到的血清TNF-α和IFN-γ水平高于抗IL-18 + ConA组（P < 0.05）。同样，IL-18 + ConA组中MMP-2-RNA和金属蛋白酶组织抑制剂-1-mRNA的表达水平高于抗IL-18 + ConA组（P < 0.05）。这些细胞因子大多由CD4(+)T细胞分泌。