The University of Southampton
University of Southampton Institutional Repository

Monocyte-astrocyte networks regulate matrix metalloproteinase gene expression and secretion in central nervous system tuberculosis in vitro and in vivo.

Harris, James E., Nuttall, Robert K., Elkington, Paul T., Green, Justin A., Horncastle, Donna E., Graeber, Manuel B., Edwards, Dylan R. and Friedland, Jon S. (2007) Monocyte-astrocyte networks regulate matrix metalloproteinase gene expression and secretion in central nervous system tuberculosis in vitro and in vivo. Journal of Immunology, 178, (2), pp. 1199-1207. (PMID:17202385).

Record type: Article

Abstract

CNS tuberculosis (CNS-TB) is the most deadly form of tuberculous disease accounting for 10% of clinical cases. CNS-TB is characterized by extensive tissue destruction, in which matrix metalloproteinases (MMPs) may play a critical role. We investigated the hypothesis that Mycobacterium tuberculosis activates monocyte-astrocyte networks increasing the activity of key MMPs. We examined the expression of all human MMPs and the tissue inhibitors of metalloproteinases (TIMPs) in human astrocytes stimulated by conditioned medium from M. tuberculosis-infected monocytes (CoMTB). Real-time RT-PCR showed that gene expression of MMP-1, -2, -3, -7, and -9 was increased (p < 0.05). MMP-9 secretion was significantly up-regulated at 24 h and increased over 120 h (p < 0.01). MMP-1, -3, and -7 secretion was not detected. Secretion of MMP-2 was constitutive and unaffected by CoMTB. Astrocyte gene expression and secretion of TIMP-1 was not affected by CoMTB although TIMP-2 secretion increased 3-fold at 120 h. Immunohistochemical analysis of human brain biopsies confirmed that astrocyte MMP-9 secretion is a predominant feature in CNS-TB in vivo. Dexamethasone inhibited astrocyte MMP-9, but not TIMP-1/2 secretion in response to CoMTB. CoMTB stimulated the nuclear translocation of NF-kappaB, inducing a 6-fold increase in nuclear p65 and a 2-fold increase in nuclear p50. This was associated with degradation of IkappaBalpha and beta within 30 min, persisting for 24 h. In summary, networks active between monocytes and astrocytes regulate MMP-9 activity in tuberculosis and astrocytes are a major source of MMP-9 in CNS-TB. Astrocytes may contribute to a matrix degrading environment within the CNS and subsequent morbidity and mortality.

Full text not available from this repository.

More information

Published date: 15 January 2007
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 341062
URI: http://eprints.soton.ac.uk/id/eprint/341062
ISSN: 0022-1767
PURE UUID: 0214c55e-4d60-4cbd-b716-8c550e61b252
ORCID for Paul T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 12 Jul 2012 10:33
Last modified: 18 Jul 2017 05:39

Export record

Contributors

Author: James E. Harris
Author: Robert K. Nuttall
Author: Justin A. Green
Author: Donna E. Horncastle
Author: Manuel B. Graeber
Author: Dylan R. Edwards
Author: Jon S. Friedland

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×