探討IL-37於免疫媒介之肝臟疾病之免疫調控作用

林佳儀

doi:10.6342/NTU201702089

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探讨IL-37於免疫媒介之肝脏疾病之免疫调控作用

Study on the Immunomodulatory Effects of IL-37 in Immune-Mediated Liver Diseases

林佳仪 , 硕士　　导师：庄雅惠　　

繁体中文 DOI： 10.6342/NTU201702089

IL-37 ；肝脏免疫疾病；原发性胆汁性胆管炎；急性肝损伤； AAV ； IL-37 ； immune-mediated liver disease ； primary biliary cholangitis ； acute liver injury ； AAV

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摘要 │ 参考文献 (91) │ 国际计量

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IL-37 is an anti-inflammatory cytokine that regulates innate immunity in vitro and shows benefits in many inflammatory disease models in vivo. However, the effects of IL-37 in immune-mediated liver diseases are still unclear. Primary biliary cholangitis (PBC) is an autoimmune disease that mainly occurs in intrahepatic bile ducts with immune cell infiltration, resulting in portal inflammation, followed by liver fibrosis, cirrhosis and eventually liver failure. Innate immunity plays a critical role in the natural history of PBC. In this study, we constructed and generated adeno-associated virus expressing human IL-37 (AAV-hIL-37) to investigate the effects of IL-37 in murine PBC. Mice were given AAV-hIL-37 three days before 2-OA-OVA immunization and PBC features were examined at 5 and 11 weeks post first immunization. Our results showed that AAV-IL-37 did not alleviate the liver inflammation of PBC mice. Autoantibodies, liver infiltrating cells and inflammatory cytokines were no differences between PBC mice administered with AAV-hIL-37 and AAV-mock. By adding culture supernatants of AAV-hIL-37 or AAV-mock transfected 293 cells to LPS stimulated thioglycollate-elicited peritoneal macrophages, we surprisingly found the culture supernatants of AAV-hIL-37 transfected cells significantly increased IL-6 secretion of macrophages. We then further investigated the effects of AAV-hIL-37 in another immune-mediated injury, concanavalin A (Con-A) induced hepatitis model. Mice were given AAV-hIL-37 or AAV-mock before Con-A injection. We found that the numbers of liver infiltrating immune cells and the frequencies of NK cells, NKT cells, dendritic cells (DC) and polymorphic nuclear cells (PMNs) were significantly increased in the liver of AAV-hIL-37 administered Con-A mice. In addition, serum IFN- of Con-A mice receiving AAV-hIL-37 was increased as soon at 1 hour after Con-A injection. Taken together, these results suggested that AAV-hIL-37 did not affect PBC whereas increased the inflammation in the liver of Con-A induced hepatitis. The immunoregulatory functions of IL-37 in the liver immune-mediated diseases need further careful studies.

参考文献 ( 91 ) 〈TOP〉

1. Dunn, E., et al., Annotating genes with potential roles in the immune system: six new members of the IL-1 family. Trends Immunol, 2001. 22(10): p. 533-6.
2. Busfield, S.J., et al., Identification and gene organization of three novel members of the IL-1 family on human chromosome 2. Genomics, 2000. 66(2): p. 213-6.
3. Kumar, S., et al., Identification and initial characterization of four novel members of the interleukin-1 family. J Biol Chem, 2000. 275(14): p. 10308-14.
4. Pan, G., et al., IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp. Cytokine, 2001. 13(1): p. 1-7.
5. Smith, D.E., et al., Four new members expand the interleukin-1 superfamily. J Biol Chem, 2000. 275(2): p. 1169-75.

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引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。