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

MAP激酶途径是信号传导各种细胞反应的基础。这一途径对免疫反应特别重要。细胞因子信号传导、趋化性和增殖。PAC-1是一种MAP激酶磷酸酶，是该途径的重要调节剂。使用Affyscore GeneChips对各种免疫细胞进行的广泛基因分析将PAC-1鉴定为活化肥大细胞中的高度调节分子。肥大细胞是重要的炎症细胞，特别是对于类风湿性关节炎和哮喘。我们已经证明，PAC-1缺陷小鼠在类风湿性关节炎小鼠模型中受到高度保护，免受炎症和疾病的影响。这项资助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，并建立PAC-1抑制疾病的基础。这项研究应该将PAC-1确立为炎症性疾病的一个新的重要靶点，提供对炎症过程的理解，并可能改善类风湿性关节炎等疾病的治疗方法。

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.