ID: 194: Role of microRNAs in signal transduction pathways of the inflammatory cytokine Interleukin-6: Relevance for liver diseases
ID: 194: Role of microRNAs in signal transduction pathways of the inflammatory cytokine Interleukin-6: Relevance for liver diseases
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ID：194：microRNA 在炎症细胞因子 Interleukin-6 信号转导途径中的作用：与肝脏疾病的相关性
DOI：
10.1016/j.cyto.2015.08.198
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发表时间：
--
期刊：
影响因子：
3.8
通讯作者：
I. Behrmann
中科院分区：
文献类型：
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作者：
Servais;M. Kirchmeyer;M. Hamsdorf;C. Haan;M. Casper;F. Lammert;P. Nazarov;L. Vallar;S. Kreis;I. Behrmann
丙型肝炎病毒（HCV）感染是全世界肝癌的主要原因之一，每年有300万至400万人受到感染。虽然一些感染者会自发根除病毒，但几乎85%的人不会，而是发展成慢性感染。最近，研究表明，具有功能性IFNL4基因的人与具有非功能性IFNL4基因的人相比，自发清除病毒或对治疗作出反应的机会更低。尽管IFNk4蛋白活性与HCV清除率差之间存在因果关系，但目前尚不清楚为什么在HCV感染期间具有功能性IFNL4基因是一种劣势。IFNk4与IFNk1、-2、3同属III型ifn。然而，它与其他的不同之处在于它的序列相似性低，而且它的分泌功能受损。这种损伤不是由于信号肽的弱，因为在IFNk3和4之间交换信号肽对分泌没有影响。当我们纯化IFNk3和4时，我们发现IFNk4比IFNk3在体外更难折叠，这表明IFNk4分泌不良可能是由于蛋白质折叠的固有问题。因为这样的问题也可能意味着IFNk4可能远比其他III型ifn不稳定，我们决定比较重组IFNk3和IFNk4的稳定性。我们的研究结果表明，IFNk4和IFNk3一样，一旦折叠得当，就会出奇地稳定。http://dx。doi。org/10.1016/j。阶段。2015.08. 195
Hepatitis C virus (HCV) infection is one of the major causes of liver cancer worldwide and every year 3–4 million people become infected. Whereas some infected people eradicate the virus spontaneously, almost 85% do not and instead develop a chronic infection. Recently, it was shown that people with a functional IFNL4 gene have a lower chance of clearing the virus spontaneously or in response to treatment than people with a non-functional IFNL4 gene. Why it is a disadvantage to have a functional IFNL4 gene during HCV infection is currently not known although a causal relationship between the activity of the IFNk4 protein and poor HCV clearance has been demonstrated. IFNk4 belongs to the type III IFNs together with IFNk1,-2, and-3. However, it differs from the others not only by its low sequence similarity but also by its impaired secretion. This impairment is not due to a weak signal peptide, as swapping the signal peptides between IFNk3 and-4 had no effect on secretion. When we purified IFNk3 and-4, we found that IFNk4 is far more difficult to refold in vitro than IFNk3 suggesting that the poor secretion of IFNk4 could be due to an inherent problem of folding the protein. Because such a problem could also mean that IFNk4 could be far unstable than the other type III IFNs, we decided to compare the stability of recombinant IFNk3 and IFNk4. Our results demonstrate that IFNk4 like IFNk3 is surprisingly stable once it has folded properly. http://dx. doi. org/10.1016/j. cyto. 2015.08. 195