The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Elkington, P. T. G.
Right arrow Articles by Friedland, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Elkington, P. T. G.
Right arrow Articles by Friedland, J. S.
The Journal of Immunology, 2005, 175: 5333-5340.
Copyright © 2005 by The American Association of Immunologists

Mycobacterium tuberculosis Up-Regulates Matrix Metalloproteinase-1 Secretion from Human Airway Epithelial Cells via a p38 MAPK Switch1

Paul T. G. Elkington*, Jenny E. Emerson*, Laura D. C. Lopez-Pascua*, Cecilia M. O’Kane*, Donna E. Horncastle{dagger}, Joseph J. Boyle{dagger} and Jon S. Friedland2,*

* Department of Infectious Diseases and {dagger} Department of Histopathology, Imperial College, London, United Kingdom

Pulmonary cavitation is vital to the persistence and spread of Mycobacterium tuberculosis (MTb), but mechanisms underlying this lung destruction are poorly understood. Fibrillar type I collagen provides the lung’s tensile strength, and only matrix metalloproteinases (MMPs) can degrade it at neutral pH. We investigated MTb-infected lung tissue and found that airway epithelial cells adjacent to tuberculosis (Tb) granulomas expressed a high level of MMP-1 (interstitial collagenase). Conditioned media from MTb-infected monocytes (CoMTb) up-regulated epithelial cell MMP-1 promoter activity, gene expression, and secretion, whereas direct MTb infection did not. CoMTb concurrently suppressed tissue inhibitor of metalloprotease-1 (TIMP-1) secretion, further promoting matrix degradation, and in Tb patients very low TIMP-1 expression was detected. MMP-1 up-regulation required synergy between TNF-{alpha} and G protein-coupled receptor signaling pathways. CoMTb stimulated p38 MAPK phosphorylation, and this is the point of TNF-{alpha} synergy with G protein-coupled receptor activation. Furthermore, p38 phosphorylation was the switch up-regulating MMP-1 activity and decreasing TIMP-1 secretion. Activated p38 localized to MMP-1-secreting airway epithelial cells in Tb patients. These data reveal a monocyte-epithelial cell network whereby MTb may drive tissue destruction, and they demonstrate that p38 phosphorylation is a key regulatory point in the generation of a matrix-degrading phenotype.




This article has been cited by other articles:


Home page
 ThoraxHome page
D O'Toole, P Hassett, M Contreras, B D Higgins, S T W McKeown, D F McAuley, T O'Brien, and J G Laffey
Hypercapnic acidosis attenuates pulmonary epithelial wound repair by an NF-{kappa}B dependent mechanism
Thorax, November 1, 2009; 64(11): 976 - 982.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Rand, J. A. Green, L. Saraiva, J. S. Friedland, and P. T. G. Elkington
Matrix Metalloproteinase-1 Is Regulated in Tuberculosis by a p38 MAPK-Dependent, p-Aminosalicylic Acid-Sensitive Signaling Cascade
J. Immunol., May 1, 2009; 182(9): 5865 - 5872.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
P. T. Elkington, J. A. Green, J. E. Emerson, L. D. Lopez-Pascua, J. J. Boyle, C. M. O'Kane, and J. S. Friedland
Synergistic Up-Regulation of Epithelial Cell Matrix Metalloproteinase-9 Secretion in Tuberculosis
Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 431 - 437.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. M. O'Kane, J. J. Boyle, D. E. Horncastle, P. T. Elkington, and J. S. Friedland
Monocyte-Dependent Fibroblast CXCL8 Secretion Occurs in Tuberculosis and Limits Survival of Mycobacteria within Macrophages
J. Immunol., March 15, 2007; 178(6): 3767 - 3776.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
J. E. Harris, J. A. Green, P. T. Elkington, and J. S. Friedland
Monocytes infected with Mycobacterium tuberculosis regulate MAP kinase-dependent astrocyte MMP-9 secretion
J. Leukoc. Biol., February 1, 2007; 81(2): 548 - 556.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. E. Harris, M. Fernandez-Vilaseca, P. T. G. Elkington, D. E. Horncastle, M. B. Graeber, and J. S. Friedland
IFN{gamma} synergizes with IL-1{beta} to up-regulate MMP-9 secretion in a cellular model of central nervous system tuberculosis
FASEB J, February 1, 2007; 21(2): 356 - 365.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
K. J. Greenlee, Z. Werb, and F. Kheradmand
Matrix Metalloproteinases in Lung: Multiple, Multifarious, and Multifaceted
Physiol Rev, January 1, 2007; 87(1): 69 - 98.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. W. Yew and C. C. Leung
Update in tuberculosis 2005.
Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 491 - 498.
[Full Text] [PDF]

Home page
 ThoraxHome page
P T G Elkington and J S Friedland
Matrix metalloproteinases in destructive pulmonary pathology
Thorax, March 1, 2006; 61(3): 259 - 266.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.