The role of PAC-1 in leukocyte activation and inflammatory responses

PAC-1在白细胞活化和炎症反应中的作用

• 批准号: nhmrc : 276411
• 负责人: Dr Shane Grey
• 金额: $ 31.06万
• 依托单位: Garvan 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-pac-1-inflammatory-responses/96004
• 关键词: role; PAC; leukocyte; activation; inflammatory

The MAP kinase pathway is fundamental for signalling a variety of cellular responses. This pathway is particularly important for immune responses ie. cytokine signalling, chemotaxis, and proliferation. PAC-1, a MAP kinase phosphatase, is an important regulator of this pathway. Extensive gene profiling of various immune cells using Affymetrix GeneChips identified PAC-1 as a highly regulated molecule in activated mast cells. Mast cells are important inflammatory cells, particularly for rheumatoid arthritis and asthma. We have shown that PAC-1 deficient mice are highly protected from inflammation and disease in a mouse model of rheumatoid arthritis. This grant aims to extend these exciting initial findings to other inflammatory diseases, particularly asthma and type 1 Diabetes, and to establish the basis for PAC-1 inhibition of disease. This research should establish PAC-1 as a new and important target for inflammatory disease, provide understanding on inflammatory processes, and possibly lead to improved therapies for diseases such as rheumatoid arthritis.

MAP激酶通路是信号转导多种细胞反应的基础。这一途径对免疫反应特别重要。细胞因子信号、趋化和增殖。PAC-1是一种MAP激酶磷酸酶，是该途径的重要调节因子。使用Affymetrix GeneChips对各种免疫细胞进行广泛的基因图谱分析，发现PAC-1是激活的肥大细胞中的一个高度调控的分子。肥大细胞是重要的炎症细胞，特别是对类风湿性关节炎和哮喘来说。我们已经证明，在类风湿性关节炎的小鼠模型中，PAC-1缺陷小鼠可以高度保护自己免受炎症和疾病的侵袭。这笔赠款旨在将这些令人兴奋的初步发现扩展到其他炎症性疾病，特别是哮喘和1型糖尿病，并为PAC-1抑制疾病奠定基础。这项研究应该确立PAC-1作为炎症性疾病的新的重要靶点，提供对炎症过程的理解，并可能导致改善类风湿性关节炎等疾病的治疗。