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- Title
1α,25-dihydroxyvitamin D<sub>3</sub> inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection.
- Authors
Coussens, Anna; Timms, Peter M.; Boucher, Barbara J.; Venton, Timothy R.; Ashcroft, Anthony T.; Skolimowska, Keira H.; Newton, Sandra M.; Wilkinson, Katalin A.; Davidson, Robert N.; Griffiths, Christopher J.; Wilkinson, Robert J.; Martineau, Adrian R.
- Abstract
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)2D3 on the secretion of interleukin-10 (IL-10) and prostaglandin E2 (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.
- Publication
Immunology, 2009, Vol 127, Issue 4, p539
- ISSN
0019-2805
- Publication type
Academic Journal
- DOI
10.1111/j.1365-2567.2008.03024.x