白介素－22在肝脏脂肪变性过程中的保护作用
文献类型：学位论文
| 作者 | 杨玲 |
| 学位类别 | 博士 |
| 答辩日期 | 2010-05-11 |
| 授予单位 | 中国科学院上海生命科学研究院营养科学研究所 |
| 授予地点 | 中国科学院上海生命科学研究院 |
| 导师 | 陈雁 |
| 关键词 | IL-22 肝脏脂肪变性 脂质代谢 IL-22R1 STAT3 |
| 学位专业 | 生物化学与分子生物学 |
| 中文摘要 | 白介素22（IL-22）是IL-10家族的一个成员，主要在Th17细胞中高度表达。此外，NKT细胞、γδT细胞、NK细胞、LTi细胞和CD8+细胞中也有IL-22的表达。IL-22与其他Th17细胞分泌的细胞因子一起在宿主防御和炎症反应中发挥了重要作用。IL-22的特异性受体IL-22R1局限于外周组织表达，而免疫细胞不表达该受体，因此，IL-22主要作用于外周组织细胞。前期的研究表明，IL-22在T细胞介导的免疫反应性肝损伤中具有保护作用。然而，目前还没有IL-22影响肝脏脂质代谢方面的研究。我们的研究首次揭示了IL-22在高脂饮食诱导的肝脏脂肪变性过程中的保护功能。重组小鼠IL-22蛋白能够刺激HepG2细胞和小鼠肝脏中STAT3磷酸化。把IL-22R1胞内段与STAT3结合位点进行突变会影响IL-22对STAT3的激活。IL-22在4小时之内即可降低脂肪生成相关基因。高脂诱导的C57BL/6小鼠和ob/ob小鼠经过一段时间的IL-22蛋白的治疗，肝脏中甘油三酯和胆固醇水平显著下降，同时ALT和AST也伴随着下降。另外，肝脏中TNFα的mRNA水平也显著下降。这些数据表明IL-22对肝脏脂肪变性有保护作用，而且很可能是通过下调脂肪生成相关基因和炎症因子TNFα共同实现的。总之，我们的研究揭露了IL-22除了在宿主防御和炎症方面的功能外对脂肪肝也有保护作用，并且提示IL-22是继IL-6、IL-10、IL-1β等参与炎症与代谢共同信号通路之外的又一新的蛋白，而IL-22受体的组织特异性表达则使IL-22可能成为一个更好的治疗肝脏脂质代谢疾病的工具。 |
| 索取号 | D2010-060 |
| 英文摘要 | Interleukin-22 (IL-22) is a Th17-related cytokine within the IL-10 family and plays an important role in host defense and inflammatory responses in orchestration with other Th17 cytokines. IL-22 exerts its functions in non-immune cells as its functional receptor IL-22RA1 is restricted in peripheral tissues but not in immune cells. It was recently found that IL-22 serves as a protective molecule to counteract the destructive nature of the T cell-mediated immune response to liver damage. However, it is currently unknown whether IL-22 has an effect in lipid metabolism in the liver. In this study, we provide evidence that IL-22 possesses a protective role in alleviating hepatic steatosis induced by high fat diet (HFD). Administration of recombinant murine IL-22 (rmIL-22) was able to stimulate STAT3 phosphorylation in HepG2 cells and mouse liver. The activation of STAT3 by rmIL-22 was reduced by the over-expression of a dominant negative IL-22R1. Short-term treatment with rmIL-22 decreased lipogenesis-related genes including critical transcription factors and enzymes for lipid synthesis in the liver. The levels of triglyceride and cholesterol in the liver were significantly reduced by long-term treatment of rmIL-22 in HFD animal models including C57BL/6 and ob/ob mice. The HFD-induced increases of ALT and AST in ob/ob mice were ameliorated by rmIL-22 treatment. Collectively, these data indicate that IL-22, in addition to its known functions in host defense and inflammation, has a protective role in hepatic steatosis likely via its regulation on lipid metabolism and inflammation in the liver. And suggest that IL-22 is another new addition to the gene which taking part in a common inflammatory and metabolic signaling pathway, such as IL-6, IL-10 and IL-1β. What’s more, the IL-22 receptor specific expression suggesting that IL-22 may be a better tool in the treatment of liver diseases. |
| 语种 | 中文 |
| 源URL | [http://202.127.25.144/handle/331004/117]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_信号转导与营养相关疾病研究组 |
| 推荐引用方式 GB/T 7714 | 杨玲. 白介素－22在肝脏脂肪变性过程中的保护作用[D]. 中国科学院上海生命科学研究院. 中国科学院上海生命科学研究院营养科学研究所. 2010. |
入库方式： OAI收割
来源：上海营养与健康研究所
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