Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in Guinea pigs.

@article{Selman2003MatrixMI,
  title={Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in Guinea pigs.},
  author={Mois{\'e}s Selman and Jos{\'e} Cisneros-Lira and Miguel Gaxiola and Remedios Ram{\'i}rez and Elizabeth M. Kudlacz and Peter G. Mitchell and Annie Pardo},
  journal={Chest},
  year={2003},
  volume={123 5},
  pages={
          1633-41
        }
}
STUDY OBJECTIVE To evaluate the effect of CP-471,474 (Pfizer Global Research and Development; Groton, CT), a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) in an experimental model of emphysema. DESIGN Randomized, double-blinded, controlled experiment. SETTING Biochemistry and morphology laboratories and animal research facility. METHODS Guinea pigs were exposed to cigarette smoke over 1 month, 2 months, and 4 months, and half of the animals received CP-471,474. Age-matched… 

Figures and Tables from this paper

An MMP-9/-12 Inhibitor Prevents Smoke-induced Emphysema and Airway Remodeling in Guinea Pigs
TLDR
The idea that MMPs are important mediators of the anatomic changes behind COPD in humans is strengthened, and MMP-9 and M MP-12 may be potential intervention targets are suggested.
ROLE FOR CATHEPSIN K IN EMPHYSEMA IN SMOKE-EXPOSED GUINEA PIGS
TLDR
A 3-fold increase in cathepsin K activity in the lungs of smoke-exposed guinea pigs likely constitutes a critical event leading to the disruption of lung extracellular matrix in this model.
Increase of Matrix Metalloproteinases in Woodsmoke-Induced Lung Emphysema in Guinea Pigs
TLDR
Results support a role of metalloproteinases and apoptosis in emphysema secondary to woodsmoke exposure in guinea pigs exposed to smoke produced by 60 g/day of pine wood.
Effect of simvastatin on MMPs and TIMPs in cigarette smoke-induced rat COPD model
TLDR
Investigation of the expression of matrix metalloproteinase (MMP)-8, M MP-9, MMP-12, tissue inhibitor of MMP (TIMP)-1, and TIMP-4 in rat lung tissues in response to CSE and the effect of simvastatin in regulating expression of M MPs and TIMPs found it blocked cigarette smoke-induced MMP8 and -9 protein synthesis.
An Inhaled Matrix Metalloprotease Inhibitor Prevents Cigarette Smoke-Induced Emphysema in the Mouse
TLDR
It is shown that an inhaled broad-spectrum matrix metalloprotease inhibitor, ilomastat, can provide protection against the development of emphysema in cigarette smoke-treated mice, and the data suggest that this class of drugs could be used practically to treat cigarette smoking-related chronic obstructive pulmonary disease by modifying the course of the disease.
Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs
TLDR
The finding that an MMP-9/MMP-12 inhibitor can substantially ameliorate morphological emphysema, small airway remodelling and the functional consequences of these lesions in a non-murine species strengthens the idea that MMPs are important mediators of the anatomical changes behind COPD in humans.
Inhaled Recombinant Alpha 1-Antitrypsin Ameliorates Cigarette Smoke-Induced Emphysema in the Mouse
TLDR
It is shown that inhaled recombinant alpha 1-antitrypsin (rAAT) can provide significant protection against the development of emphysema in cigarette smoke-treated mice, suggesting that rAAT inhalation therapy might represent a practical approach towards treating emphySEma in humans, by modifying the course of the disease.
Anti-inflammatory effects of celecoxib in rat lungs with smoke-induced emphysema.
TLDR
The findings suggest that the anti-inflammatory effects of celecoxib are mediated by its effects on NF-kappaB-regulated gene expression, which ultimately reduces the progression of CS-induced pulmonary emphysema.
Proteases and emphysema
TLDR
The idea that a single protease or a single type of inflammatory cell is responsible for human emphysema is unlikely to be true; rather, there are complex interactions among proteases, and between proteases and other mediators.
Matrix metalloproteinases in emphysema.
...
...

References

SHOWING 1-10 OF 37 REFERENCES
Tobacco smoke-induced lung emphysema in guinea pigs is associated with increased interstitial collagenase.
TLDR
It is strongly suggested that increased interstitial collagen degradation plays a role in the development of lung emphysema.
Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients.
TLDR
The presence of increased levels of matrix metalloproteinases in the lungs of patients with emphysema is demonstrated for the first time and it is suggested that, in BAL fluid, collagenase activity may be a better indicator of the presence of emphySEma than elastase.
Matrix metalloproteinases 2, 9, and 13, and tissue inhibitors of metalloproteinases 1 and 2 in experimental lung silicosis.
TLDR
It is suggested that an imbalance in the expression of MMPs and TIMPs may be implicated in extracellular matrix remodeling and basement membrane disruption during experimental lung silicosis.
Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis.
  • A. Janoff
  • Biology, Medicine
    The American review of respiratory disease
  • 1985
TLDR
Assessments of lung elastase inhibitors in humans continue to support the importance of alpha-1-proteinase inhibitor in the protection of the lower respiratory tract, but newer information on locally produced, low molecular weight elastsase inhibitors indicates that these, too, may play a significant role.
Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema.
TLDR
The lung is altered in emphysema such that the Type II pneumocyte secretes MMP-1 and the induction of a proteolytic enzyme within the Type 2 pneumocyte suggests that the cells within the lung itself are capable of producing degradative enzymes in this disease process.
Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor.
TLDR
Almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro are reviewed, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 2-PI at the molecular and functional levels are reviewed.
Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema.
TLDR
It is demonstrated that IL-13 is a potent stimulator of MMP and cathepsin-based proteolytic pathways in the lung and causes emphysema with enhanced lung volumes and compliance, mucus metaplasia, and inflammation, when inducibly overexpressed in the adult murine lung.
Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice.
TLDR
Administration of an MMP inhibitor attenuates early left ventricular dilation after experimental MI in mice, and the effects of MMP inhibition on the changes in end-systolic area and end-diastolic area were most prominent in animals that had more initialleft ventricular dilatation.
Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD.
TLDR
Findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.
...
...