Ulanova Marina, Duta Florentina, Puttagunta Lakshmi, Schreiber Alan D, Befus A Dean
University of Alberta, Department of Medicine, Edmonton, Alberta, T6G 2S2, Canada.
Expert Opin Ther Targets. 2005 Oct;9(5):901-21. doi: 10.1517/14728222.9.5.901.
Allergic asthma and rhinitis are prevalent diseases in the modern world, both marked by inflammation of the airways. The spleen tyrosine kinase (Syk) plays a critical role in the regulation of such immune and inflammatory responses. Although Syk is best known as a key component of immunoreceptor signalling complexes in leukocytes, recent studies demonstrated Syk expression in cells outside the haematopoietic lineage. Moreover, in recent years, it has been established that Syk is involved in various signalling cascades including those originating from integrin and cytokine receptors. Thus, Syk likely has a much wider biological role than previously recognised. Specific inhibition of Syk using aerosolised antisense oligonucleotides in liposome complexes significantly decreased lung inflammatory responses in experimental asthma and acute lung injury models. In addition, pharmacological inhibitors of Syk have been recently developed with potential for use as therapeutics. However, in the development and the rational delivery of drugs targeting Syk, it is important to consider the multiple cell types that express this kinase and the potential effects of its inhibition on various physiological functions. This review focuses on the recent data and the emerging ideas about Syk as a therapeutic target.
过敏性哮喘和鼻炎是现代社会中的常见疾病，两者均以气道炎症为特征。脾酪氨酸激酶（Syk）在调节此类免疫和炎症反应中起关键作用。尽管Syk作为白细胞免疫受体信号复合物的关键成分最为人所知，但最近的研究表明其在造血谱系以外的细胞中也有表达。此外，近年来已证实Syk参与多种信号级联反应，包括那些源自整合素和细胞因子受体的反应。因此，Syk可能具有比先前认识到的更为广泛的生物学作用。在实验性哮喘和急性肺损伤模型中，使用脂质体复合物包裹的雾化反义寡核苷酸特异性抑制Syk可显著降低肺部炎症反应。此外，最近已开发出Syk的药理学抑制剂，具有用作治疗药物的潜力。然而，在开发和合理递送靶向Syk的药物时，重要的是要考虑表达这种激酶的多种细胞类型及其抑制对各种生理功能的潜在影响。本综述重点关注关于Syk作为治疗靶点的最新数据和新出现的观点。
