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Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.

Brilha, S; Chong, DLW; Khawaja, AA; Ong, CWM; Guppy, NJ; Porter, JC; Friedland, JS (2018) Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis. Front Immunol, 9. p. 1348. ISSN 1664-3224 https://doi.org/10.3389/fimmu.2018.01348
SGUL Authors: Friedland, Jonathan Samuel

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Abstract

Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB.

Item Type: Article
Additional Information: © 2018 Brilha, Chong, Khawaja, Ong, Guppy, Porter and Friedland. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: extracellular matrix, integrins, matrix metalloproteinases, respiratory epithelial cell, tuberculosis, tuberculosis, extracellular matrix, respiratory epithelial cell, matrix metalloproteinases, integrins, Science & Technology, Life Sciences & Biomedicine, Immunology, tuberculosis, extracellular matrix, respiratory epithelial cell, matrix metalloproteinases, integrins, MYCOBACTERIUM-TUBERCULOSIS, EXTRACELLULAR-MATRIX, CELL-MIGRATION, ALPHA(2)BETA(1) INTEGRIN, ALPHA-3-BETA-1 INTEGRIN, MMP-1 EXPRESSION, WOUND REPAIR, P38 MAPK, LUNG, KERATINOCYTES
Journal or Publication Title: Front Immunol
ISSN: 1664-3224
Language: eng
Dates:
DateEvent
22 June 2018Published
31 May 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
PubMed ID: 29988449
Web of Science ID: WOS:000436132900001
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110623
Publisher's version: https://doi.org/10.3389/fimmu.2018.01348

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