Imperial College London
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DrAkifKhawaja

Faculty of Medicine, National Heart & Lung Institute

Research Associate
 
 
 
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Contact

 

akif.khawaja10 Website

 
 
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Location

 

525ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Dos:2018:10.3389/fimmu.2018.01348,
author = {Dos, Santos Brilha S and Chong, D and Khawaja, A and Ong, C and Guppy, N and Porter, J and Friedland, J},
doi = {10.3389/fimmu.2018.01348},
journal = {Frontiers in Immunology},
title = {Integrin α2β1 expression regulates matrix metalloproteinase-1-dependent bronchial epithelial repair in pulmonary tuberculosis},
url = {http://dx.doi.org/10.3389/fimmu.2018.01348},
volume = {9},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Dos,Santos Brilha S
AU  - Chong,D
AU  - Khawaja,A
AU  - Ong,C
AU  - Guppy,N
AU  - Porter,J
AU  - Friedland,J
DO  - 10.3389/fimmu.2018.01348
PY  - 2018///
SN  - 1664-3224
TI  - Integrin α2β1 expression regulates matrix metalloproteinase-1-dependent bronchial epithelial repair in pulmonary tuberculosis
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2018.01348
UR  - http://hdl.handle.net/10044/1/60506
VL  - 9
ER  -
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