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J. Biol. Chem., Vol. 276, Issue 44, 41417-41423, November 2, 2001
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From the Departments of Pediatrics, Medicine, and Cell Biology and
Physiology, Washington University School of Medicine,
St. Louis, Missouri 63110
Matrilysin (matrix metalloproteinase-7) is
expressed by mucosal epithelia throughout the body and functions in
host defense by activating murine intestinal
Regulation of Matrilysin Expression in Airway
Epithelial Cells by Pseudomonas aeruginosa Flagellin*
-defensins. In normal
adult human lung, matrilysin is expressed at low levels in the airway
epithelium, but is markedly up-regulated in cystic fibrosis (CF).
Because CF lungs support a heavy bacterial load, we assessed if
relevant CF pathogens regulate matrilysin expression in human lung
epithelial cells. Indeed, acute infection with Pseudomonas
aeruginosa (but not Staphylococcus aureus,
Haemophilus influenzae, or Klebsiella pneumoniae) induced the expression of matrilysin in Calu-3 lung epithelial cells. Increased matrilysin mRNA levels were detectable at 3 h post-infection and peaked at a 25-fold induction between 6 and 8 h. Both P. aeruginosa CF isolates and laboratory
strains induced matrilysin expression to similar levels. Flagellin, the monomeric precursor of bacterial flagella, was identified as the inductive factor released by P. aeruginosa that regulated
matrilysin expression. In addition, flagellin-null mutants failed to
stimulate matrilysin expression in cultured cells or in lungs infected
in vivo. These data show that P. aeruginosa
(and specifically flagellin) potently stimulates matrilysin expression
in lung epithelial cells and may mediate the overexpression of this
proteinase in CF lungs.
*
This work was supported by National Institutes of Health
Grants HL54619 and HL29594 (to W. C. P.) and DE14040 (to C. L. W.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Pediatrics,
Campus Box 8208, Washington University, 660 S. Euclid Ave., St. Louis,
MO 63110. Tel.: 314-286-2862; Fax: 314-286-2894; E-mail: parks_w@kids.wustl.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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