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J Infect Dis. 2016 Feb 15;213(4):618-27. doi: 10.1093/infdis/jiv458. Epub 2015 Sep 27.

Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis.

Author information

1
Infectious Diseases and Immunity, Imperial College London Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore.
2
Department of Molecular Biology, Umeå University, Sweden.
3
Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore.
4
Immunobiology Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
5
Infectious Diseases Pathogenesis Section, Comparative Medicine Branch, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
6
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore.
7
Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, South Korea.
8
Infectious Diseases and Immunity, Imperial College London.
9
Infectious Diseases and Immunity, Imperial College London Faculty of Medicine, University of Southampton, United Kingdom.

Abstract

Cavitation in tuberculosis enables highly efficient person-to-person aerosol transmission. We performed transcriptomics in the rabbit cavitary tuberculosis model. Among 17 318 transcripts, we identified 22 upregulated proteases. Five type I collagenases were overrepresented: cathepsin K (CTSK), mast cell chymase-1 (CMA1), matrix metalloproteinase 1 (MMP-1), MMP-13, and MMP-14. Studies of collagen turnover markers, specifically, collagen type I C-terminal propeptide (CICP), urinary deoxypyridinoline (DPD), and urinary helical peptide, revealed that cavitation in tuberculosis leads to both type I collagen destruction and synthesis and that proteases other than MMP-1, MMP-13, and MMP-14 are involved, suggesting a key role for CTSK. We confirmed the importance of CTSK upregulation in human lung specimens, using immunohistochemical analysis, which revealed perigranulomatous staining for CTSK, and we showed that CTSK levels were increased in the serum of patients with tuberculosis, compared with those in controls (3.3 vs 0.3 ng/mL; P = .005).

KEYWORDS:

RNAseq; cathepsin K; collagen; collagenolysis; rabbit; tuberculosis

PMID:
26416658
PMCID:
PMC4721912
DOI:
10.1093/infdis/jiv458
[Indexed for MEDLINE]
Free PMC Article

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