Wolf Marlene, Albrecht Stefan, Märki Christa
Theodor Kocher Institute, University of Bern, Freiestrasse 1, CH-3012 Bern, Switzerland.
Int J Biochem Cell Biol. 2008;40(6-7):1185-98. doi: 10.1016/j.biocel.2007.12.009. Epub 2007 Dec 28.
Chemokines are small, secreted proteins that orchestrate the migration of cells, which are involved in immune defence, immune surveillance and haematopoiesis. However, chemokines are also implicated in the pathology of various inflammatory diseases, cancers and HIV. The chemokine system is considerably large and has a redundancy in the repertoire of its inflammatory mediators. Therefore, strict regulation of chemokine activity is crucial. Chemokines are the substrate for various proteases including the serine protease CD26/dipeptidyl-peptidase IV and matrix metalloproteinases. Regulation by proteolytic cleavage controls and fine-tunes chemokine function by either enhancing or reducing its chemotactic activity or receptor selectivity. Often chemokines and the proteases that regulate them are produced in the same microenvironment and expression of both may be simultaneously induced by a common stimulus enabling the rapid regulation of chemokine activity. The overall impact of cleaved chemokines in cellular responses is very complex. In this review, we will give an overview on chemokine modification and the respective chemokine modifying proteases. Furthermore, we will summarize the emerging literature describing the consequences in inflammation, haematopoiesis, cancer and HIV infection upon proteolytic chemokine processing.
趋化因子是一类小分子分泌蛋白，可协调细胞迁移，这些细胞参与免疫防御、免疫监视和造血过程。然而，趋化因子也与各种炎症性疾病、癌症和艾滋病的病理过程有关。趋化因子系统相当庞大，其炎症介质库存在冗余。因此，严格调控趋化因子活性至关重要。趋化因子是包括丝氨酸蛋白酶CD26/二肽基肽酶IV和基质金属蛋白酶在内的多种蛋白酶的作用底物。通过蛋白水解切割进行的调控通过增强或降低趋化因子的趋化活性或受体选择性来控制和微调趋化因子功能。趋化因子及其调控蛋白酶通常在同一微环境中产生，二者的表达可能由共同刺激同时诱导，从而实现趋化因子活性的快速调控。裂解后的趋化因子对细胞反应的总体影响非常复杂。在本综述中，我们将概述趋化因子修饰及相应的趋化因子修饰蛋白酶。此外，我们还将总结新出现的文献，这些文献描述了蛋白水解处理趋化因子后在炎症、造血、癌症和艾滋病感染方面的后果。
