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Monocyte-dependent oncostatin M and TNF-? synergize to stimulate unopposed matrix metalloproteinase-1/3 secretion from human lung fibroblasts in tuberculosis

Record type: Article

Leukocyte-derived matrix metalloproteinases (MMP) are implicated in the tissue destruction characteristic of tuberculosis (TB). The contribution of lung stromal cells to MMP activity in TB is unknown. Oncostatin M (OSM) is an important stimulus to extrapulmonary stromal MMP induction, but its role in regulation of pulmonary MMP secretion or pathophysiology of TB is unknown. We investigated OSM secretion from Mycobacterium tuberculosis (Mtb)-infected human monocytes/macrophages and the networking effects of such OSM on lung fibroblast MMP secretion. Mtb increased monocyte OSM secretion dose dependently in vitro. In vivo tuberculous granulomas immunostained positively for OSM. Further, conditioned media from Mtb-infected monocytes (CoMTb) induced monocyte OSM secretion (670 +/- 55 versus 166 +/- 14 pg/mL in controls), implicating an autocrine loop. Mtb-induced OSM secretion was prostaglandin (PG) sensitive, and required activation of surface G-protein coupled receptors. OSM induction was ERK MAP kinase dependent, p38-requiring but JNK-independent. OSM synergized with TNF-alpha, a key cytokine in TB granuloma formation, to stimulate pulmonary fibroblast MMP-1/-3 secretion, while suppressing secretion of tissue inhibitors of metalloproteinases-1/-2. In summary, Mtb infection of monocytes results in PG-dependent OSM secretion, which synergizes with TNF-alpha to drive functionally unopposed fibroblast MMP-1/-3 secretion, demonstrating a previously unrecognized role for OSM in TB.

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Citation

O'Kane, Cecilia M., Elkington, Paul T. and Friedland, Jon S. (2008) Monocyte-dependent oncostatin M and TNF-? synergize to stimulate unopposed matrix metalloproteinase-1/3 secretion from human lung fibroblasts in tuberculosis European Journal of Immunology, 38, (5), pp. 1321-1330. (doi:10.1002/eji.200737855). (PMID:18398932).

More information

Published date: April 2008
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 341058
URI: http://eprints.soton.ac.uk/id/eprint/341058
ISSN: 0014-2980
PURE UUID: 9450b21d-5d56-49a3-88a0-d52cbdbc5703
ORCID for Paul T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

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Date deposited: 12 Jul 2012 10:09
Last modified: 18 Jul 2017 05:39

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Contributors

Author: Cecilia M. O'Kane
Author: Jon S. Friedland

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