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Regulation of lung fibroblast and epithelial cell apoptosis by cyclooxygenase-2 and prostaglandin E2 and their role in the pathogenesis of pulmonary fibrosis. (360G-Wellcome-078073_Z_05_Z)

Pulmonary fibrosis represents the end stage of a heterogeneous group of conditions with poor prognosis and no effective treatment. Recent studies suggest increased epithelial cell (EC) apoptosis and fibroblast resistance to apoptosis contributes to the pathogenesis of fibrosis but the mechanisms are incompletely understood. However, the host laboratory has shown that patients with idiopathic pulmonary fibrosis (IPF) have a decreased capacity to synthesise cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2). COX-2/PGE2 induce fibroblast apoptosis and protect epithelial cells from apoptosis but their role in regulating apoptosis in fibrotic lung is unknown. I therefore hypothesise that the decreased capacity to induce COX-2/PGE2 in patients with IPF contributes to pathogenesis by increasing EC apoptosis and decreasing fibroblast apoptosis. To address this hypothesis I will determine whether COX-2/PGE2 deficiency contributes to human fibrotic lung fibroblast resistanceto apoptosis and induction of EC apoptosis in vitro. I will also examine the effect of COX-2 deficiency on EC and fibroblast apoptosis in an animal model


06 Dec 2005

Grant details
Amount Awarded 242197
Applicant Surname Maher
Approval Committee Clinical Interview Committee
Award Date 2005-12-06T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Research Training Fellowship
Internal ID 078073/Z/05/Z
Lead Applicant Prof Toby Maher
Planned Dates: End Date 2009-05-31T00:00:00+00:00
Planned Dates: Start Date 2006-04-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Geoffrey Laurent
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