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Macrophage elastase (MMP-12): a pro-inflammatory mediator?
Soazig Nénan1, Elisabeth Boichot, Vincent Lagente
1Pfizer Global R&D, Fresnes Laboratories, Fresnes, France.
Memorias Do Instituto Oswaldo Cruz
|June 18, 2005
Summary
Macrophage elastase (MMP-12) drives airway inflammation and cell recruitment in mice, mimicking features of COPD. This MMP-12 mouse model aids in evaluating new anti-inflammatory treatments.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Biochemistry
Background:
- Macrophage elastase (MMP-12) degrades extracellular matrix and is implicated in pulmonary diseases like COPD.
- Limited data existed on MMP-12's direct role in airway inflammation.
Purpose of the Study:
- To investigate the pro-inflammatory role of MMP-12 in the airways.
- To establish a mouse model for evaluating anti-inflammatory drugs.
Main Methods:
- Instillation of recombinant human MMP-12 (rhMMP-12) into mouse airways.
- Analysis of inflammatory cell recruitment (neutrophils, macrophages) and cytokine levels.
- Assessment of drug effects (dexamethasone, rolipram, marimastat).
Main Results:
- rhMMP-12 instillation caused significant neutrophil and macrophage recruitment.
- Pro-inflammatory cytokines and gelatinases increased following rhMMP-12 exposure.
- Epithelial cells may be a key target of rhMMP-12.
- Tested anti-inflammatory drugs partially reversed the induced inflammation.
Conclusions:
- The rhMMP-12 mouse model effectively replicates key inflammatory aspects of COPD.
- MMP-12 plays a pro-inflammatory role in the airways.
- This model is valuable for preclinical assessment of novel anti-inflammatory therapies for COPD and related lung diseases.