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

Center for Lung Biology,¹ Department of Genome Sciences,² Department of Pediatrics, University of Washington, Seattle, Washington 98109,³ Pulmonary and Critical Care Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109⁴

Received 11 June 2007/ Returned for modification 12 September 2007/ Accepted 27 September 2007

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.

Published ahead of print on 8 October 2007.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Camilli