ROLE OF PROTEASE ACTIVATED RECEPTORS IN CYSTIC FIBROSIS LUNG PATHOLOGY

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/110245

Funding Status
Closed

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Funded Activity Summary

Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the respiratory epithelium. These, in turn, stimulate the movement of neutrophils from the blood to the lung where damage then ensues. How these proteases stimulate release is unclear but studies suggest other proteases involved in inflammation induce release through their interaction with a novel group of protease activated receptors (PAR). In this study, we wish to determine whether PAR are activated or inactivated by host and bacterial proteases commonly seen in the lungs of CF patients. If PAR are activated, it may be possible to develop antagonists which target specific PARS to modulate respiratory epithelial cell function. If inactivated, preservation by adjunct protease inhibitor treatment may be highly beneficial. We will use in vitro technology and cells derived from non-CF and CF patients. This study has great potential in the development of adjunct anti-inflammatory therapy for the treatment of both CF and other inflammatory lung diseases.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $176,521.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Respiratory Diseases

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Burkholderia cepacia | Cell physiology | Cystic fibrosis | Epithelial cells | Inflammation | Medical bacteriology | Medical biochemistry : proteins and peptides | Pseudomonas aeruginosa | Respiratory diseases

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