Protease-activated receptors as potential drug targets in allergic airways disease

Funded Activity Summary

Asthma is a lung disease that kills about 700 Australians each year and causes widespread morbidity in our community. For people with allergic asthma inhalation of allergens such as those contained in house dust triggers an immune response that causes swelling of the airway wall, overproduction of mucus and bronchial smooth muscle contraction. These effects lead to the narrowing of the airways that makes breathing more difficult in people with asthma. Our research groups have been investigating a novel group of proteins, called protease-activated receptors (PARs), and in an exciting development have found that substances that stimulate PARs inhibit allergic airways inflammation in mice, which is a well-established animal model of allergic asthma. This raises the possibility that PAR stimulants may in the future be developed as anti-asthma drugs. However, there are many large gaps in our understanding of airway PARs that need to be filled before their use as anti-asthma drugs can be contemplated. Thus, the current study will address many important questions: Do PAR stimulants always improve allergic inflammation, or are there some doses or times of dosing that worsen allergic inflammation? Stimulants of one PAR, called PAR2, improve allergic inflammation, but what about stimulants of the three other PARs (PAR1, PAR3 and PAR4) that exist in the airways? How do PARs improve allergic inflammation, and which substances and cells are involved? Are PAR stimulants also effective in more complex animal models of allergic inflammation, such as those involving proteolytic allergens (e.g. Der p1 from the house dust mite), respiratory tract viruses, and extended periods of allergen exposure (chronic models) that better reflect the human disease allergic asthma? The answers to these and a range of other questions will significantly improve our understanding of the potential utility of PAR stimulants in the treatment of allergic airways disease.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $469,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Pharmacology and Pharmaceutical Sciences

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Airway inflammation | Allergic airway inflammation | Allergy | Asthma | Prostaglandin E2 | Protease-activated receptors | Respiratory pharmacology

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