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Inhibition of matrix metalloproteinase-9 reduces clinical severity in a murine model of Multiple Sclerosis

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Date Issued:
2015
Summary:
Matrix metalloproteinases MMPs are a family of proteolytic enzymes that mediate the degradation of various components of the extracellular matrix. Their functions are essential for normal physiological processes such as wound healing, but their dysregulation is associated with various pathologies including autoimmune diseases such as Multiple Sclerosis MS. Experimental Autoimmune Encephalomyelitis EAE is a well-established murine model of MS that is mediated by CD4 T-cells. These cells penetrate the blood-brain-barrier BBB, recruit other immune cells, initiate destruction of the myelin sheath, and cause axonal loss. MMP-9 is a hallmark enzyme in progression of MS that is required for penetration of the BBB and generation of autoantigens in EAE. In addition, recent studies have demonstrated that MMP-9 contributes to normal intracellular function of various cell types including antigen activated T-cells; however, the intracellular role of MMP-9 in immune cell activation during EAE pathogenesis is not known. In this study, we used a highly selective MMP-9 triple-helical peptide inhibitor THPI that is a phosphinate transition state analog to examine antigen specific T-cell responses. We found that selective inhibition of MMP-9 can mitigate pathogenic T-cell activity and cellular trafficking as well as the clinical severity of EAE, suggesting that selective MMP-9 inhibition in MS can be a potent therapeutic option.
Title: Inhibition of matrix metalloproteinase-9 reduces clinical severity in a murine model of Multiple Sclerosis.
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Name(s): Onwuha-Ekpete, Lillian C.
Tokmina-Roszyk, Dorota
Fields, Gregg B.
Graduate College
Type of Resource: text
Genre: Poster
Date Created: 2015
Date Issued: 2015
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 1 p.
Language(s): English
Summary: Matrix metalloproteinases MMPs are a family of proteolytic enzymes that mediate the degradation of various components of the extracellular matrix. Their functions are essential for normal physiological processes such as wound healing, but their dysregulation is associated with various pathologies including autoimmune diseases such as Multiple Sclerosis MS. Experimental Autoimmune Encephalomyelitis EAE is a well-established murine model of MS that is mediated by CD4 T-cells. These cells penetrate the blood-brain-barrier BBB, recruit other immune cells, initiate destruction of the myelin sheath, and cause axonal loss. MMP-9 is a hallmark enzyme in progression of MS that is required for penetration of the BBB and generation of autoantigens in EAE. In addition, recent studies have demonstrated that MMP-9 contributes to normal intracellular function of various cell types including antigen activated T-cells; however, the intracellular role of MMP-9 in immune cell activation during EAE pathogenesis is not known. In this study, we used a highly selective MMP-9 triple-helical peptide inhibitor THPI that is a phosphinate transition state analog to examine antigen specific T-cell responses. We found that selective inhibition of MMP-9 can mitigate pathogenic T-cell activity and cellular trafficking as well as the clinical severity of EAE, suggesting that selective MMP-9 inhibition in MS can be a potent therapeutic option.
Identifier: FA00005904 (IID)
Collection: FAU Student Research Digital Collection
Note(s): The Sixth Annual Graduate Research Day was organized by Florida Atlantic University’s Graduate Student Association. Graduate students from FAU Colleges present abstracts of original research and posters in a competition for monetary prizes, awards, and recognition.
Held by: Florida Atlantic University Libraries
Sublocation: Digital Library
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00005904
Use and Reproduction: Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.