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Repeated endotoxin exposure induces interstitial fibrosis associated with enhanced gelatinase (MMP-2 and MMP-9)

M Corbel1, N Theret, S Caulet-Maugendre

  • 1INSERM U 456, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, France.

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|May 8, 2001
PubMed
Abstract

Insights

Chronic lung inflammation in mice exposed to lipopolysaccharide (LPS) led to pulmonary fibrosis. Matrix metalloproteinases (MMPs) in bronchoalveolar lavage fluid correlated with this lung injury, suggesting their role in fibrosis development.

Area of Science:

  • Pulmonary medicine
  • Immunology
  • Biochemistry

Background:

  • Matrix metalloproteinases (MMPs) dysregulation is linked to lung injury in inflammatory conditions.
  • Pulmonary fibrosis is a significant lung disease associated with MMPs.

Purpose of the Study:

  • To investigate the relationship between MMP activity in bronchoalveolar lavage fluid and collagen deposition in lung tissue.
  • To analyze MMPs in a murine model of lipopolysaccharide (LPS)-induced chronic inflammation.

Main Methods:

  • Mice (BP2) were exposed to repeated aerosols of E. coli lipopolysaccharide (LPS) for 8 months.
  • Analyzed inflammatory reactions, collagen deposition, and MMP-2 and MMP-9 levels in bronchoalveolar lavage (BAL) fluid.

Main Results:

  • LPS exposure induced chronic inflammation and collagen deposition in alveolar walls after 10 weeks.
  • MMP-9 induction correlated with neutrophil recruitment in BAL fluid.
  • MMP-2 levels increased during both early inflammation and fibrotic phases.

Conclusions:

  • Repeated LPS aerosol exposure can induce pulmonary interstitial fibrosis in mice.
  • MMPs appear to be involved in the development of LPS-induced pulmonary fibrosis.

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