In:
The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 41.14-41.14
Abstract:
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that mediate the degradation of extracellular matrix components and are crucial for normal physiological processes; however, their dysregulation has been implicated in numerous pathologies associated with autoimmunity as well as neurological disorders. MMP-28 is the least characterized member of this family and it has been implicated as a regulator of myelination during neural development and repair. Moreover, recent studies have suggested a role for MMP-28 in determining the strength of the immune response. To unravel the complex role of MMP-28 in an autoimmune neurodegenerative disease such as Multiple Sclerosis (MS) we utilized the Experimental Autoimmune Encephalomyelitis (EAE) murine model. We compared disease progression in both WT and MMP-28 null mice and did not observe significant difference between both groups. However, weight loss and therefore disease severity was overall higher in MMP-28 null mice. Subsequently, we subjected brain samples from both WT and MMP-28 null to global protein profiling using a shotgun proteomics approach and corresponding protein profiles were compared. Our findings, provide further evidence that MMP-28 is an important factor in the autoimmune response. Moreover, in addition to the expected impact of MMP-28 on various proteins associated with myelin, we identified mitochondrial protein complexes that were upregulated in samples derived from MMP-28 null mice. These data provide evidence of a previously unknown intracellular role of MMP-28 and suggest a possible novel mechanism of immune regulation. Our data suggest that MMP-28 might be an important antitarget in autoimmune neurodegenerative diseases such as MS.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.200.Supp.41.14
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2018
detail.hit.zdb_id:
1475085-5
