In:
The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 180.8-180.8
Abstract:
Matrix Metalloproteinase -28 (MMP-28) is the newest and least characterized member of the matrixins family of proteolytic enzymes. These enzymes are associated with the degradation of the extracellular matrix affiliated with both physiological and pathological processes, including immune responses. In similar fashion to the rest of MMP family, a vast amount of literature on MMP-28 addresses its’ extracellular role. This study highlights the intracellular role of MMP-28 in macrophages, specifically its ability to modulate cellular energetics and consequently influence M0, M1, and M2 phenotype polarization. In our preliminary studies, we utilized shotgun proteomics profiling of WT and MMP-28 null mice under both healthy conditions and following experimental autoimmune encephalomyelitis (EAE) induction. We identified two mitochondrial protein complexes dysregulated in MMP-28 null mice. We then isolated bone marrow derived macrophages to further elucidate differences using the Seahorse mitochondrial and glycolytic stress assays. We found that MMP-28 alters mitochondrial respiration and glycolysis across all tested phenotypes (M0, M1, and M2). Moreover, our preliminary data emphasis a significant role for MMP-28 in the efficient utilization of various fuel sources during mitochondrial respiration. Our findings show, for the first time, that MMP-28 has a profound effect on cellular bioenergetics affecting both oxidative phosphorylation, glycolytic pathways, and efficient macrophage activation. This suggests the potential of MMP-28 as both an immunomodulatory agent to further study macrophage bioenergetics and a therapeutic agent for pathologies associated with macrophages.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.202.Supp.180.8
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2019
detail.hit.zdb_id:
1475085-5
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