Ys. Lopez-boado et al., Regulation of matrilysin expression in airway epithelial cells by Pseudomonas aeruginosa flagellin, J BIOL CHEM, 276(44), 2001, pp. 41417-41423
Matrilysin (matrix metalloproteinase-7) is expressed by mucosal epithelia t
hroughout the body and functions in host defense by activating murine intes
tinal a-defensins. In normal adult human lung, matrilysin is expressed at l
ow 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 epit
helial cells. Indeed, acute infection with Pseudomonas aeruginosa (but not
Staphylococcus aureus, Haemophilus influenzae, or Klebsiella pneumoniae) in
duced the expression of matrilysin in Calu-3 lung epithelial cells. Increas
ed 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 an
d laboratory strains induced matrilysin expression to similar levels. Flage
llin, the monomeric precursor of bacterial flagella, was identified as the
inductive factor released by P. aeruginosa that regulated matrilysin expres
sion. In addition, flagellin-null mutants failed to stimulate matrilysin ex
pression in cultured cells or in lungs infected in vivo. These data show th
at P. aeruginosa (and specifically flagellin) potently stimulates matrilysi
n expression in lung epithelial cells and may mediate the overexpression of
this proteinase in CF lungs.