Deficiency of interleukin-19 exacerbates lipopolysaccharide/D-galactosamine-induced acute liver failure.
Deficiency of interleukin-19 exacerbates lipopolysaccharide/D-galactosamine-induced acute liver failure.
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DOI：
10.1292/jvms.20-0344
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发表时间：
2020-10-20
期刊：
影响因子：
--
通讯作者：
Azuma YT
中科院分区：
文献类型：
--
作者：
Fujimoto Y;Kuwamura M;Azuma YT
白细胞介素（IL）-19是聚集在IL-20细胞因子超家族中的细胞因子，其具有抗炎和促炎两个方面，这取决于炎性疾病的病因。IL-19的功能已在皮肤和炎症性肠道疾病中进行了评估，但尚未在肝脏疾病中进行研究。在这里，我们研究了IL-19对急性肝衰竭（ALF）的影响，使用两种ALF小鼠模型：脂多糖和D-半乳糖胺（LPS/GalN）诱导的模型和刀豆球蛋白A（ConA）诱导的模型。在LPS/GalN诱导的ALF模型中，这主要是由肝脏巨噬细胞的先天性免疫应答引起的，IL-19敲除（KO）小鼠显示与野生型（WT）小鼠相比肝偏离酶、天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的血浆水平增加。在肝脏切片的组织病理学中，与WT小鼠相比，IL-19 KO小鼠加重了肝损伤，肝脏中有明显的出血性病变和肝细胞死亡。在该模型中，与WT小鼠相比，IL-19 KO小鼠肝组织中促炎趋化因子CCL 2和CCL 5的mRNA表达增加。LPS/GalN诱导肝组织IL-19及其受体亚单位mRNA表达。然而，在由CD 4 + T细胞活化诱导的ConA诱导的ALF模型中，WT和IL-19 KO之间的肝损伤没有差异。这些数据表明，IL-19对炎症介导的肝损伤具有保护作用，这取决于病因。
Interleukin (IL)-19 is a cytokine clustered in the IL-20 cytokine superfamily with both anti-inflammatory and pro-inflammatory aspects depending on the etiology of inflammatory disease. The function of IL-19 has been evaluated in cutaneous and inflammatory bowel diseases, but has not been studied in liver diseases. Here, we examined the effect of IL-19 on acute liver failure (ALF) using two mouse models of ALF: lipopolysaccharide and D-galactosamine (LPS/GalN)-induced model and concanavalin A (ConA)-induced model. In the LPS/GalN-induced ALF model, which is mainly caused by the innate immune response of liver macrophages, IL-19 knockout (KO) mice showed increased plasma level of liver deviation enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with wild-type (WT) mice. In histopathology of liver sections, IL-19 KO mice exacerbated liver injury with marked hemorrhagic lesions and hepatocellular death in the liver compared with WT mice. In this model, mRNA expressions of pro-inflammatory chemokines, CCL2 and CCL5 were increased in liver tissue from IL-19 KO mice compared with WT mice. Moreover, the mRNA expressions of IL-19 and its receptor subunit were induced in liver tissue by LPS/GalN administration. However, there is no difference in liver injury between WT and IL-19KO in the ConA-induced ALF model induced by CD4+ T cell activation. These data suggest that IL-19 has a protective effect against inflammation-mediated liver injury, which is dependent on the etiology.
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影响因子：
7.3
作者：
Niess JH;Hruz P;Kaymak T
通讯作者：
Kaymak T
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：
25.7
作者：
通讯作者：
--
影响因子：
4
作者：
Zimmermann HW;Trautwein C;Tacke F
通讯作者：
Tacke F
影响因子：
3.8
作者：
Maes M;Vinken M;Jaeschke H
通讯作者：
Jaeschke H