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Matrix Metalloproteinase Inhibition in a Murine Model of Cavitary Tuberculosis Paradoxically Worsens Pathology

Year: 2018
Type: article
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.
DOI: 10.1093/infdis/jiy373
Authors: Alvaro A Ordonez, Supriya Pokkali, Julian Sanchez-Bautista, Mariah H Klunk, Michael E Urbanowski, André Kübler, William R Bishai, Paul T Elkington, Sanjay K Jain
Institutions: Johns Hopkins University, Johns Hopkins Medicine, National Health Service, Barking, Havering And Redbridge University Hospitals NHS Trust, Queen's Hospital, University of Southampton
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W2808969867
FWCI: 3.397
Cites: 15
Cited by: 31
Related to: 10