Mechanisms of protease-activated receptor-2-mediated bronchoprotection

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/114256

Funding Status
Closed

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Funded Activity Summary

The incidence of asthma continues to increase globally, yet there have been few real therapeutic advances. Our research, however, has recently uncovered a novel mechanism that protects the airways from inflammatory diseases like asthma. We have found that the layer of cells that line the airways - the epithelium - acts as a detector of early inflammatory events and releases anti-inflammatory substances. The lungs achieve this level of protection via 'sensor' molecules called receptors which are located in the epithelium. In the case of our discovery, these receptors are called protease-activated receptors (PARs) to highlight the unique manner in which they are turned on or activated by enzymes called proteases. We have discovered that the epithelium of the lungs stores these enzymes and probably releases them during the inital stages of infection. Once released, these enzymes are detected by PARs on epithelial cells which then release substances that inhibit multiple inflammatory pathways. This mechanism protects the airways from effects that make breathing difficult, as in asthma. We have confirmed that this system provides protection in the airways of intact animals. The purpose of this projects outlined in this application is to examine the effects of activating one PAR, PAR2, on several processes in the lung, in order to characterise the individual events and processes that underlie the protective response. These studies will enable us to determine whether synthetic compounds that activate PAR2 are potential novel compounds for the treatment of diseases like asthma.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $354,758.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical biochemistry - carbohydrates

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Airway epithelium | Airway function | Asthma | Bronchitis | Bronchoprotective mechanisms | Prostaglandins | Protease activated receptors | Pulmonary inflammation

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