Diminished Prostaglandin E2Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis

• DOI: 10.1164/rccm.200905-0674oc
• Publication Date: 2010-03-05T03:42:55Z
• Authors: Toby M. Maher; Iona C. Evans; Stephen E. Bottoms; Paul F. Mercer; Andrew J. Thorley; Andrew G. Nicholson; Geoffrey J. Laurent; Teresa D. Tetley; Rachel C. Chambers; Robin J. McAnulty
• Keywords: Fas ligand

Rationale: Patients with idiopathic pulmonary fibrosis (IPF), a progressive disease dismal prognosis, exhibit an unexplained disparity of increased alveolar epithelial cell (AEC) apoptosis but reduced fibroblast apoptosis.Objectives: To examine whether the failure patients IPF to up-regulate cyclooxygenase (COX)-2, and thus antifibrotic mediator prostaglandin (PG)E2, accounts for this imbalance.Methods: Fibroblasts primary type II AECs were isolated from control fibrotic human lung tissue. The effects COX-2 inhibition exogenous PGE2 on AEC sensitivity Fas ligand (FasL)-induced assessed.Measurements Main Results: fibroblasts are resistant FasL-induced compared fibroblasts. Inhibition in resulted apoptosis-resistant phenotype. Administration almost doubled rate FasL alone. Conversely, AECs, protected against apoptosis. In and, greater extent, fibroblasts, inhibits phosphorylation Akt, suggesting that regulation prosurvival protein kinase is important mechanism by which modulates cellular apoptotic responses.Conclusions: observation deficiency results provides novel pathogenic insight into mechanisms driving persistent fibroproliferation IPF.