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Individual Matrix Metalloproteinases Control Distinct Transcriptional Responses in Airway Epithelial Cells Infected with Pseudomonas aeruginosa

Kassim, Sean Y., Gharib, Sina A., Mecham, Brigham H., Birkland, Timothy P., Parks, William C., McGuire, John K.
Infection and immunity 2007 v.75 no.12 pp. 5640-5650
Pseudomonas aeruginosa, cell culture, cell death, cystic fibrosis, epithelial cells, epithelium, gene expression, gene expression regulation, genes, genomics, host-pathogen relationships, immune response, matrilysin, mice, pathogens, pneumonia, signal transduction, transcription (genetics)
Airway epithelium is the initial point of host-pathogen interaction in Pseudomonas aeruginosa infection, an important pathogen in cystic fibrosis and nosocomial pneumonia. We used global gene expression analysis to determine airway epithelial transcriptional responses dependent on matrilysin (matrix metalloproteinase 7 [MMP-7]) and stromelysin-2 (MMP-10), two MMPs induced by acute P. aeruginosa pulmonary infection. Extraction of differential gene expression (EDGE) analysis of gene expression changes in P. aeruginosa-infected organotypic tracheal epithelial cell cultures from wild-type, Mmp7⁻/⁻, and Mmp10⁻/⁻ mice identified 2,091 matrilysin-dependent and 1,628 stromelysin-2-dependent genes that were differentially expressed. Key node network analysis showed that these MMPs controlled distinct gene expression programs involved in proliferation, cell death, immune responses, and signal transduction, among other host defense processes. Our results demonstrate discrete roles for these MMPs in regulating epithelial responses to Pseudomonas infection and show that a global genomics strategy can be used to assess MMP function.