Novel posttranslational modifications of gelatinase B/matrix metalloproteinase-9

Gelatinase B or matrix metalloproteinase-9 (MMP-9) is the most studied metalloproteinase and has gained significant scientific interest as a target enzyme in inflammatory and vascular diseases. This status is linked to expression of variant MMP-9 forms by almost all cell types, tight regulation of the enzyme and of its specific inhibitor (TIMP-1) by cytokines and other inflammatory mediators, roles in processes of development and angiogenesis and in diseases such as cancer, autoimmune and hypersensitivity reactions. For their migration through tissues, leukocytes need MMP-9, because in single MMP-9 gene knockout mice this migration is reduced. However, little is known about collagenolysis in vivo, or about other MMP-9-mediated processes. This project aims to (i) broaden our biochemical and biological knowledge about variant MMP-9 forms from leukocytes (ii) explore the roles of the inflammatory or adaptive immunological micro-environments on posttranslational modifications of MMP-9 and the functional consequences and (iii) place the new information within the contexts of acute inflammatory (neutrophil biology, endotoxinemia) and long-term adaptive (lymphocytes, chronic experimental autoimmune encephalomyelitis, EAE) immune reactions with the use of animal models and analysis of blood and tissue specimens from well-defined patient cohorts.

Keywords:metalloproteinase-9, posttranslational, modifications, gelatinase, B/matrix

Disciplines:Immunology