The role of SOCS-1 and SOCS-3 in regulating acute inflammatory arthritis.

SOCS-1 和 SOCS-3 在调节急性炎症性关节炎中的作用。

• 批准号: nhmrc : 305523
• 负责人: Dr Ian Campbell
• 金额: $ 29.67万
• 依托单位: The Walter and Eliza Hall Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-socs-1-inflammatory-arthritis/82217
• 关键词: role; SOCS; regulating; acute; inflammatory

Rheumatoid arthritis (RA) is a chronic inflammatory disease which mainly targets joints. The disease causes chronic joint pain, stiffness and loss of joint mobility, leading to increasing difficulty in carrying out day to day activities. Treatment for RA has gradually improved, but remains inadequate for many patients. Although the cause is unknown, progress has been made in understanding the molecular pathways which drive RA. The disease is characterised by the production of high levels of inflammatory mediators called cytokines. This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice, although a significant number of patients fail to respond to treatment. An alternative approach to develop new treatments for RA would be to use the body's natural inhibitors to limit the actions of inflammatory cytokines. One such inhibitor is Suppressor of Cytokine Signalling-1 (SOCS-1). Using animal models, we have shown that mice lacking SOCS-1 develop more severe arthritis and have identified the different cell types it acts on. Further studies are still needed before SOCS-1 can be developed as a treatment for RA. We aim to identify the major cell type responsible for the increased severity of disease seen when SOCS-1 is absent. This will allow for treatment to be targetted to the most appropriate cells in the joint. We also aim to study the related molecule SOCS-3, to see whether it has similar effects on inhibiting the severity of disease. These studies will provide more information on the activity of SOCS proteins during inflammatory diseases in general and RA in particular and and may lead to new approaches for the treatment of RA.

类风湿性关节炎（RA）是一种以关节为主要靶点的慢性炎症性疾病。这种疾病会导致慢性关节疼痛、僵硬和关节活动性丧失，导致日常活动越来越困难。类风湿关节炎的治疗已经逐渐改善，但对许多患者来说仍然不足。虽然原因不明，但在理解驱动RA的分子途径方面取得了进展。这种疾病的特征是产生高水平的称为细胞因子的炎症介质。这一发现导致了特异性细胞因子抑制剂的开发并将其引入临床实践，尽管大量患者对治疗没有反应。另一种开发RA新疗法的方法是使用人体的天然抑制剂来限制炎性细胞因子的作用。一种这样的抑制剂是细胞因子信号传导抑制因子-1（SOCS-1）。使用动物模型，我们已经表明，缺乏SOCS-1的小鼠发展更严重的关节炎，并确定了它作用于不同的细胞类型。在SOCS-1可以开发为治疗RA之前，仍需要进一步的研究。我们的目的是确定负责增加疾病的严重程度时，SOCS-1是缺席的主要细胞类型。这将允许治疗针对关节中最合适的细胞。我们还旨在研究相关分子SOCS-3，看看它是否对抑制疾病的严重程度具有类似的作用。这些研究将提供更多关于SOCS蛋白在炎症性疾病中的活性的信息，特别是RA，并可能导致治疗RA的新方法。