Synergistic up-regulation of epithelial cell matrix metalloprotemase-9 secretion in tuberculosis

Paul T. Elkington, Justin A. Green, Jenny E. Emerson, Laura D. Lopez-Pascua, Joseph J. Boyle, Cecilia M. O'Kane, Jon S. Friedland*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


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 mitogen-activated protein kinase (MAPK) by SB203580 (P < 0.01) and 48.3% by inhibition of extracellular signal-regulated kinase with PD98059 (P < 0.05). MMP-9 secretion was prostaglandin independent. TNF-α 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-α to increase MMP-9 secretion by NHBE 6-fold (P < 0.01 compared with 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.

Original languageEnglish
Pages (from-to)431-437
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number4
Publication statusPublished - 01 Oct 2007
Externally publishedYes


  • Epithelial cell
  • Matrix metalloproteinase
  • Tuberculosis

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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