Repeated endotoxin exposure induces interstitial fibrosis associated with enhanced gelatinase (MMP-2 and MMP-9) activity.
BACKGROUND
Dysregulation of matrix metalloproteinases (MMPs) has been implicated in lung injury associated with inflammatory disorders and several lung diseases such as pulmonary fibrosis.


OBJECTIVE
We studied a murine model of lipopolysaccharide (LPS)-induced chronic inflammation in order to analyse the relationship between MMP activity in bronchoalveolar lavage fluid and collagen deposition in lung tissue. BP2 mice were exposed to repeated aerosols of LPS of E. coli for 8 months.


RESULTS
The inflammatory reaction induced by LPS increased throughout the time of exposure and was associated after 10 weeks with collagen deposition in the alveolar walls. Meantime, we observed in BAL fluid from LPS-exposed mice an early induction of MMP-9 correlated with neutrophil recruitment. MMP-2 increased during the early inflammatory phase, and also during the development of the fibrotic phase.


CONCLUSIONS
Repeated exposure of mice to an aerosol of LPS can lead to pulmonary interstitial fibrosis and MMPs seem to be associated with this process.
Corbel
M
M
INSERM U 456, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, France.
Theret
N
N
Caulet-Maugendre
S
S
Germain
N
N
Lagente
V
V
Clement
B
B
Boichot
E
E
D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
D008070:Lipopolysaccharides; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9