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Matrix metalloproteinases in pulmonary and central nervous system tuberculosis-a review

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Title: Matrix metalloproteinases in pulmonary and central nervous system tuberculosis-a review
Authors: Rohlwink, UK
Walker, NF
Ordonez, AA
Li, YJ
Tucker, EW
Elkington, PT
Wilkinson, RJ
Wilkinson, KA
Item Type: Journal Article
Abstract: Tuberculosis (TB) remains the single biggest infectious cause of death globally, claiming almost two million lives and causing disease in over 10 million individuals annually. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with various physiological roles implicated as key factors contributing to the spread of TB. They are involved in the breakdown of lung extracellular matrix and the consequent release of Mycobacterium tuberculosis bacilli into the airways. Evidence demonstrates that MMPs also play a role in central nervous system (CNS) tuberculosis, as they contribute to the breakdown of the blood brain barrier and are associated with poor outcome in adults with tuberculous meningitis (TBM). However, in pediatric TBM, data indicate that MMPs may play a role in both pathology and recovery of the developing brain. MMPs also have a significant role in HIV-TB-associated immune reconstitution inflammatory syndrome in the lungs and the brain, and their modulation offers potential novel therapeutic avenues. This is a review of recent research on MMPs in pulmonary and CNS TB in adults and children and in the context of co-infection with HIV. We summarize different methods of MMP investigation and discuss the translational implications of MMP inhibition to reduce immunopathology.
Issue Date: 18-Mar-2019
Date of Acceptance: 3-Mar-2019
URI: http://hdl.handle.net/10044/1/68658
DOI: https://dx.doi.org/10.3390/ijms20061350
ISSN: 1422-0067
Publisher: MDPI AG
Journal / Book Title: International Journal of Molecular Sciences
Volume: 20
Issue: 6
Copyright Statement: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: HIV-TB-associated IRIS
adult
central nervous system
extracellular matrix breakdown
lung
matrix metalloproteinases
pediatric
tuberculosis
tuberculous meningitis
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Chemical Physics
Publication Status: Published
Conference Place: Switzerland
Open Access location: https://www.mdpi.com/1422-0067/20/6/1350
Article Number: ARTN 1350
Appears in Collections:Department of Medicine



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