Preotease activated receptor-2 in pleural inflammation. (360G-Wellcome-071407_Z_03_A)

£62,360

Protease Activated Receptor-2 in Pleural Inflammation Pleural diseases are common in clinical practice. Pleural inflammation is a crucial process underlying the pathogenesis of most pleural diseases, but the mechanisms governing pleural inflammation are poorly understood. Evidence that protease-activated receptor (PAR)-2, a novel seven-transmembrane G-protein-coupled receptor, holds a critical role in tissue inflammation is rapidly accumulating. Our preliminary work showed that activation of PAR-2 in pleural mesothelial cells induced significant release of inflammatory cytokines and rapid pleural neutrophile recruitment in mice, supporting an urgent need to establish the role of PAR-2 in human pleural disorders. Hypothesis and Aims: We hypothesize that activation of PAR-2 in mesothelial cells is crucial to the induction of pleural inflammation in common pleural disease in humans. The aims of this project are: To establish a causal role of PAR-2 in pleural disease using PAR-2 deficient mice. To identify physiological activators (in particular Factor Xa) of PAR-2 in common pleural diseases. To confirm the role of PAR-2 in pleural disease in humans. Significance: This project presents a unique opportunity to combine the host laboratory's expertise on PARs and the applicant's interest in pleural disease, and is supported by promising preliminary work. These studies will provide valuable insight on the PAR-2-mediated organ inflammation. Establishing a causal role of PAR-2 and identifying its activators in pleural diseases may allow the design of novel therapeutic strategies.

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Grant Details

Amount Awarded 62360
Applicant Surname Lee
Approval Committee Clinical Interview Committee
Award Date 2005-12-06T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Intermediate Fellowship: Inactive scheme
Internal ID 071407/Z/03/A
Lead Applicant Dr Gary Lee
Partnership Value 62360
Planned Dates: End Date 2007-03-31T00:00:00+00:00
Planned Dates: Start Date 2006-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Rachel Chambers