| Literature DB >> 29920600 |
Alvaro A Ordonez1,2,3, Supriya Pokkali1,2,3, Julian Sanchez-Bautista1,2,3, Mariah H Klunk1,2,3, Michael E Urbanowski1,4, André Kübler5, William R Bishai1,4, Paul T Elkington6,7, Sanjay K Jain1,2,3.
Abstract
Matrix metalloproteinases (MMPs) degrade extracellular matrix and are implicated in tuberculosis pathogenesis and cavitation. In particular, MMP-7 is induced by hypoxia and highly expressed around pulmonary cavities of Mycobacterium tuberculosis-infected C3HeB/FeJ mice. In this study, we evaluated whether administration of cipemastat, an orally available potent inhibitor of MMP-7, could reduce pulmonary cavitation in M. tuberculosis-infected C3HeB/FeJ mice. We demonstrate that, compared with untreated controls, cipemastat treatment paradoxically increases the frequency of cavitation (32% vs 7%; P = .029), immunopathology, and mortality. Further studies are needed to understand the role of MMP inhibitors as adjunctive treatments for pulmonary tuberculosis.Entities:
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Year: 2019 PMID： 29920600 PMCID： PMC6601699 DOI： 10.1093/infdis/jiy373
Source DB: PubMed Journal: J Infect Dis ISSN： 0022-1899 Impact factor: 5.226