help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on June 15, 2007, doi:10.1165/rcmb.2007-0011OC

Am. J. Respir. Cell Mol. Biol., Volume 37, Number 4, October 2007, 431-437

A more recent version of this article appeared on October 1, 2007
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2007-0011OCv1
37/4/431    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 reprints & 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
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
Right arrow Articles by Friedland, J. S

Submitted on January 17, 2007
Revised on June 14, 2007

Synergistic Up-regulation of Epithelial Cell Matrix Metalloproteinase-9 Secretion in Tuberculosis

Paul T Elkington1, Justin A Green1, Jenny E Emerson1, Laura D Lopez-Pascua1, Joseph J Boyle2, Cecilia M O'Kane1, and Jon S Friedland1*

1 Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Campus, London, United Kingdom, 2 Department of Histopathology, Imperial College London, Hammersmith Campus, London, United Kingdom

* To whom correspondence should be addressed. E-mail: j.friedland{at}imperial.ac.uk.

Mycobacterium tuberculosis (MTb) kills approximately 2 million people each year. MTb must drive host tissue destruction to disseminate and also to cause pulmonary cavitation. Matrix metalloproteinase-9 (MMP-9, gelatinase B) is implicated in this Tb-related immunopathology. We demonstrate that conditioned media from MTb-infected monocytes (CoMTb) but not direct infection with MTb up-regulates MMP-9 gene expression and secretion from primary human bronchial epithelial cells (NHBE). MMP-9 secretion was increased 8.7-fold by CoMTb (p<0.05) as assayed by gelatin zymography. A549 and 16HBE14o epithelial cell MMP secretion was significantly less than primary NHBE secretion. MMP-9 secretion was decreased 53.2% by inhibition of the p38 MAPK by SB203580 (p<0.01) and 48.3% by inhibition of ERK with PD98059 (p<0.05). MMP-9 secretion was prostaglandin-independent. TNF-{alpha} was necessary but not sufficient for MMP-9 up-regulation by the monocyte-epithelial cell network. Soluble factors derived from Tb culture synergized with TNF-{alpha} to increase MMP-9 secretion by NHBE 6-fold (p<0.01 compared to either stimulus alone). Together these data reveal a new mechanism by which host- and pathogen-derived factors act together in MTb infection to drive MAPK-dependent MMP-9 secretion from respiratory epithelial cells.




This article has been cited by other articles:


Home page
 Eur Respir JHome page
S. McKeown, A. G. Richter, C. O'Kane, D. F. McAuley, and D. R. Thickett
MMP expression and abnormal lung permeability are important determinants of outcome in IPF
Eur. Respir. J., January 1, 2009; 33(1): 77 - 84.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2007 American Thoracic Society. 		  ATS Best of the Web