Regulation of cytokine mRNA stability by IL-10

IL-10 对细胞因子 mRNA 稳定性的调节

• 批准号: 72619628
• 负责人: Privatdozent Dr. Gerald Grütz
• 金额: --
• 依托单位: Institut für Medizinische Immunologie (CVK)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/72619628?language=en
• 关键词: Regulation; cytokine; mRNA; stability; IL

Cytokines are important regulators of an adequate immune response. An excessive inflammatory response can lead as much as an excessive anti-inflammatory counter regulation to life threatening situations. For an appropriate therapeutical intervention it is therefore of uppermost importance to understand the regulation of pro- and anti-inflammatory cytokines. IL-10 is one of the few cytokines which can confine an inflammation. Despite of this, there is little knowledge of how IL-10 mediates this inhibitory activity on the molecular level. We could demonstrate that IL-10 decreases the mRNA stability of several important inflammatory cytokines. The stability of mRNAs can be regulated via proteins binding to AU-rich elements in cytokine mRNAs. Furthermore, the recently discovered microRNAs have been reported to regulate mRNA stability. We have identified the IL-10 regulated gene Tis11D as a candidate for mediating the effects of IL-10 on AU-rich elements. Furthermore, we could show that IL-10 can prevent the down regulation of mi-R16. We therefore want to analyse the functional role of these factors in mRNA stability regulation of cytokine mRNAs.

细胞因子是充分免疫应答的重要调节剂。过度的炎症反应可以导致与过度的抗炎反调节一样多的危及生命的情况。因此，对于适当的治疗干预，理解促炎和抗炎细胞因子的调节是最重要的。IL-10是能够限制炎症的少数细胞因子之一。尽管如此，关于IL-10如何在分子水平上介导这种抑制活性的知识很少。我们可以证明IL-10降低了几种重要炎性细胞因子的mRNA稳定性。mRNA的稳定性可以通过与细胞因子mRNA中富含AU的元件结合的蛋白质来调节。此外，最近发现的microRNA已被报道调节mRNA的稳定性。我们已经确定了IL-10调节基因Tis 11 D作为介导IL-10对富含AU的元件的作用的候选者。此外，我们可以证明IL-10可以防止mi-R16的下调。因此，我们希望分析这些因子在细胞因子mRNA的mRNA稳定性调节中的功能作用。