Abstract

Background

Interleukin (IL)-39 is a novel member of IL-12 family and has been reported to play a pro-inflammatory role in lupus-like mice, but its function in concanavalin A (ConA)-induced liver injury is currently unclear.

Materials and methods

In this study, we investigated the effects of IL-39 expression in a mouse model of ConA induced-hepatitis. We first showed that delivery of plasmid DNA encoding mouse IL-39 using the hydrodynamic tail vein injection method increased IL-39 mRNA and protein levels in the liver. We then administrated mice with IL-39 plasmid before ConA injection and measured serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, inflammatory infiltration, and hepatocyte necrosis in the liver. Additionally, we further explored the potential mechanism of IL-39 in ConA-induced liver injury by measuring several inflammatory mediators.

Results

We found that ectopic IL-39 expression promoted the ConA-induced increase in serum ALT and AST levels, inflammatory infiltration, and hepatocyte necrosis in the liver. We also observed that IL-39 plasmid administration significantly increased serum and liver interferon-γ, tumor necrosis factor-α, and IL-17A levels, but did not affect serum and liver IL-10 levels in ConA-induced hepatitis.

Conclusion

Our results suggest that IL-39 can exacerbate ConA-induced hepatitis and may be a therapeutic target in inflammatory liver disease.

中文翻译：

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白细胞介素39加剧刀豆球蛋白A诱导的肝损伤

摘要

背景

白细胞介素 (IL)-39 是 IL-12 家族的新成员，据报道在狼疮样小鼠中发挥促炎作用，但其在伴刀豆球蛋白 A (ConA) 诱导的肝损伤中的功能目前尚不清楚。

材料和方法

在这项研究中，我们研究了 IL-39 表达对 ConA 诱导的肝炎小鼠模型的影响。我们首先表明，使用流体动力学尾静脉注射方法递送编码小鼠 IL-39 的质粒 DNA 会增加肝脏中的 IL-39 mRNA 和蛋白质水平。然后，我们在注射 ConA 之前给小鼠注射 IL-39 质粒，并测量血清丙氨酸氨基转移酶 (ALT) 和天冬氨酸氨基转移酶 (AST) 水平、炎症浸润和肝脏中的肝细胞坏死。此外，我们通过测量几种炎症介质进一步探索了 IL-39 在 ConA 诱导的肝损伤中的潜在机制。

结果

我们发现异位 IL-39 表达促进了 ConA 诱导的血清 ALT 和 AST 水平升高、炎症浸润和肝脏中的肝细胞坏死。我们还观察到，IL-39 质粒给药显着增加血清和肝脏干扰素-γ、肿瘤坏死因子-α 和 IL-17A 水平，但不影响 ConA 诱导的肝炎中血清和肝脏 IL-10 水平。

结论

我们的结果表明 IL-39 可以加剧 ConA 诱导的肝炎，并且可能是炎症性肝病的治疗靶点。