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IFN-gamma- and TNF-...
IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: The role of cathelicidin LL-37
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Martineau, Adrian R. (författare)
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Wilkinson, Katalin A. (författare)
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Newton, Sandra M. (författare)
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Floto, R. Andres (författare)
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Norman, Anthony W. (författare)
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Skolimowska, Keira (författare)
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Davidson, Robert N. (författare)
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- Sørensen, Ole E (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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Kampmann, Beate (författare)
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Griffiths, Christopher J. (författare)
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Wilkinson, Robert J. (författare)
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(creator_code:org_t)
- 2007
- 2007
- Engelska.
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Ingår i: Journal of Immunology. - 1550-6606. ; 178:11, s. 7190-7198
- Relaterad länk:
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http://www.jimmunol....
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Vitamin D deficiency is associated with susceptibility to tuberculosis, and its biologically active metabolite, 1 alpha,25 dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3), has pleiotropic immune effects. The mechanisms by which 1 alpha,25(OH)(2)D-3 protects against tuberculosis are incompletely understood. 1 alpha,25(OH)(2)D-3 reduced the growth of mycobacteria in infected human PBMC cultures in a dose-dependent fashion. Coculture with agonists or antagonists of the membrane or nuclear vitamin D receptors indicated that these effects were primarily mediated by the nuclear vitamin D receptors. 1 alpha,25(OH)(2)D-3 reduced transcription and secretion of protective IFN-gamma, IL-12p40, and TNF in infected PBMC and macrophages, indicating that 1 alpha,25(OH)(2)D-3 does not mediate protection via these cytokines. Although NOM was up-regulated by 1 alpha,25(OH)(2)D-3, inhibition of NO formation marginally affected the suppressive effect of 1 alpha,25(OH)(2)D-3 on bacillus Calmette Guerin in infected cells. By contrast, 1 alpha,25(OH)(2)D-3 strongly up-regulated the cathelicidin hCAP-18 gene, and some hCAP-18 polypeptide colocalized with CD14 in 1 alpha,25(OH)(2)D-3 stimulated PBMC, although no detectable LL-37 peptide was found in supernatants from similar 1 alpha,25(OH)(2)D-3-stimulated PBMC cultures. A total of 200 mu g/ml of the active peptide LL-37, in turn, reduced the growth of Mycobacterium tuberculosis in culture by 75.7%. These findings suggest that vitamin D contributes to protection against TB by '' nonclassical '' mechanisms that include the induction of antimicrobial peptides.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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Newton, Sandra M ...
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Floto, R. Andres
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Norman, Anthony ...
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Skolimowska, Kei ...
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Davidson, Robert ...
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Sørensen, Ole E
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Kampmann, Beate
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Griffiths, Chris ...
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Wilkinson, Rober ...
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