Integrin alpha2 beta1 modulates MMP-1expression in Tuberculosis

Abstract

Event Abstract Back to Event Integrin alpha2 beta1 modulates MMP-1expression in Tuberculosis Sara Brilha1*, Joanna C. Porter2, Heather I. Zecchini3 and Jon S. Friedland1 1 Imperial College London, Department of Infectious Diseases and Immunity, United Kingdom 2 University College London, Centre for Inflammation and Tissue Repair, United Kingdom 3 Cancer Research UK Cambridge Research Institute, Light Microscopy Facility, United Kingdom In tuberculosis (TB) Matrix Metalloproteinase-1 (MMP-1), a collagenase, has a major role in tissue destruction and cavitation (1). MMP-1 secretion is amplified by networks such as those between monocytes and respiratory epithelial cells (2). Cell adhesion to the extracellular matrix is mediated by integrins, which can coordinate rapid responses to airway injuries (3). We hypothesised that adhesion to collagen I modulates MMP-1 secretion in primary Human Bronchial Epithelial cells (NHBEs) in TB. NHBEs were stimulated with conditioned medium from Mtb-infected monocytes (CoMtb) or control medium, in the presence or absence of coated or free human collagen I. Integrin engagement was studied by neutralising anti-integrin alpha2 and alpha3 antibodies (mAbs), confocal microscopy and laser scanning cytometry. MMP-1 gene expression and secretion was measured by ELISA, Luminex, real-time PCR and functional DQ collagenase assay. CoMtb stimulated NHBEs, adherent to 100μg/ml coated collagen decreased MMP-1 secretion from 1647±65pg/mL to 1127±91pg/mL (32%). In contrast, free collagen upregulated MMP-1 by 23%. Gene expression data was consistent with secretion. Collagenolytic activity was 3-fold higher in absence of collagen than with coated collagen and 5-fold higher in the presence free collagen (p<0.05). MMP-1 suppression with coated collagen was abolished by 2mM EDTA (p>0.05). Adhesion to coated anti-alpha2 mAbs reduced MMP-1 secretion by 30% (p<0.01). Confocal microscopy showed integrin alpha2 beta1 polarization on coated collagen while free collagen I caused integrin alpha2 beta1 microclustering. In summary, MMP-1 activity, gene expression and secretion is regulated by collagen-cell interactions and integrins are potentially crucial in the control of inflammatory tissue destruction in TB. References 1- Elkington, P., T. Shiomi, R. Breen, R. K. Nuttall, C. A. Ugarte-Gil, N. F. Walker, L. Saraiva, B. Pedersen, F. Mauri, M. Lipman, D. R. Edwards, B. D. Robertson, J. D'Armiento, and J. S. Friedland. 2011. MMP-1 drives immunopathology in human tuberculosis and transgenic mice. J Clin Invest 121:1827-1833. 2-Elkington, P. T., J. E. Emerson, L. D. Lopez-Pascua, C. M. O'Kane, D. E. Horncastle, J. J. Boyle, and J. S. Friedland. 2005. Mycobacterium tuberculosis up-regulates matrix metalloproteinase-1 secretion from human airway epithelial cells via a p38 MAPK switch. J Immunol 175:5333-5340. 3-Pilewski, J. M., J. D. Latoche, S. M. Arcasoy, and S. M. Albelda. 1997. Expression of integrin cell adhesion receptors during human airway epithelial repair in vivo. Am J Physiol 273:L256-263. Keywords: Matrix Metalloproteinases, Epithelial Cells, Extracellular Matrix, Integrins, Tuberculosis Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Brilha S, Porter JC, Zecchini HI and Friedland JS (2013). Integrin alpha2 beta1 modulates MMP-1expression in Tuberculosis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00105 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Miss. Sara Brilha, Imperial College London, Department of Infectious Diseases and Immunity, London, United Kingdom, s.brilha110@imperial.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sara Brilha Joanna C Porter Heather I Zecchini Jon S Friedland Google Sara Brilha Joanna C Porter Heather I Zecchini Jon S Friedland Google Scholar Sara Brilha Joanna C Porter Heather I Zecchini Jon S Friedland PubMed Sara Brilha Joanna C Porter Heather I Zecchini Jon S Friedland Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.