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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
1α,25-dihydroxyvitamin D
3
inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection
Immunology, Volume 127, No. 4, Year 2009
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Description
Matrix metalloproteinases (MMP) can degrade all components of pulmonary extracellular matrix. Mycobacterium tuberculosis induces production of a number of these enzymes by human macrophages, and these are implicated in the pathogenesis of pulmonary cavitation in tuberculosis. The active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 [1α,25(OH) 2D3], has previously been reported to inhibit secretion of MMP-9 in human monocytes (MN), but its influence on the secretion and gene expression of MMP and tissue inhibitors of MMP (TIMP) in M. tuberculosis- infected cells has not previously been investigated. We therefore determined the effects of 1α,25(OH)2D3 on expression, secretion and activity of a number of MMP and TIMP in M. tuberculosis-infected human leucocytes; we also investigated the effect of 1α,25(OH)2D 3 on the secretion of interleukin-10 (IL-10) and prostaglandin E 2 (PGE2), both transcriptional regulators of MMP expression. We found that M. tuberculosis induced expression of MMP-1, MMP-7 and MMP-10 in MN and MMP-1 and MMP-10 in peripheral blood mononuclear cells (PBMC). 1α,25(OH)2D3 significantly attenuated M. tuberculosis-induced increases in expression of MMP-7 and MMP-10, and suppressed secretion of MMP-7 by M. tuberculosis-infected PBMC. MMP-9 gene expression, secretion and activity were significantly inhibited by 1α,25(OH) 2D3 irrespective of infection. In contrast, the effects of 1α,25(OH)2D3 on the expression of TIMP-1, TIMP-2 and TIMP-3 and secretion of TIMP-1 and TIMP-2 were small and variable. 1α,25(OH)2D3 also induced secretion of IL-10 and PGE2 from M. tuberculosis-infected PBMC. These findings represent a novel immunomodulatory role for 1α,25(OH)2D3 in M. tuberculosis infection. © 2009 Blackwell Publishing Ltd.
Authors & Co-Authors
Coussens, Anna K.
United Kingdom, London
Mrc National Institute for Medical Research
Timms, Peter M.
United Kingdom, London
Homerton University
Boucher, Barbara J.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Venton, Timothy R.
United Kingdom, London
Homerton University
Ashcroft, Anthony T.
United Kingdom, London
Homerton University
Skolimowska, Keira H.
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Newton, Sandra M.
United Kingdom, London
Imperial College London
Andrea Wilkinson, Katalin Andrea
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
Davidson, Robert N.
United Kingdom, Harrow
Northwick Park Hospital
Griffiths, Christopher J.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Wilkinson, Robert J.
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
United Kingdom, Harrow
Northwick Park Hospital
Martineau, Adrian R.
United Kingdom, London
Mrc National Institute for Medical Research
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Statistics
Citations: 127
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1111/j.1365-2567.2008.03024.x
ISSN:
00192805
e-ISSN:
13652567
Research Areas
Genetics And Genomics