Prostaglandin E(2) induces fibroblast apoptosis by modulating multiple survival pathways.

ABSTRACT: Although the lipid mediator prostaglandin E(2) (PGE(2)) exerts antifibrotic effects by inhibiting multiple fibroblast functions, its ability to regulate fibroblast survival is unknown. Here, we examined the effects of this prostanoid on apoptosis and apoptosis pathways in normal and fibrotic lung fibroblasts. As compared to medium alone, 24 h of treatment with PGE(2) increased apoptosis of normal lung fibroblasts in a dose-dependent manner (EC(50) approximately 50 nM), as measured by annexin V staining, caspase 3 activity, cleavage of poly-ADP-ribose polymerase, and single-stranded DNA levels. PGE(2) also potentiated apoptosis elicited by Fas ligand plus cycloheximide. These proapoptotic actions were dependent on signaling through the EP2/EP4 receptors and by downstream activation of both

SUBMITTER: Huang SK 

PROVIDER: S-EPMC2812040 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature