Prostaglandin E2 possesses different potencies in inducing Vascular Endothelial Growth Factor and Interleukin-8 production in COPD human lung fibroblasts

We studied the role of PGE2, its biosynthetic enzymes and its receptors, in regulating the functions of lung fibroblasts through the production of Vascular Endothelial Growth Factor(VEGF) and Interleukin-8 (IL-8) in COPD subjects. Lung fibroblasts fromControl(C)(n¼6), Smoker(HS)(n¼6) andCOPDpatients(n¼8) werecultured, and basalPGE2, VEGF,andIL-8measuredinsupernatantsbyELISA.COX-1/COX-2andEPreceptors expressionwereassessedbywesternblotandbyRT-PCR.ReleaseofVEGFandIL-8byhumanfetallung fibroblasts (HFL-1;lung,diploid,human)wasevaluatedunderdifferentconditions. PGE2, VEGF,andIL-8levels,COX-2,EP2,andEP4proteinexpressionandmRNAwereincreasedin COPD whencomparedtoControls.LowconcentrationsofsyntheticPGE2 increased thereleaseofVEGFin HFL-1,buthigherconcentrationswereneededtoinducethereleaseofIL-8.Thiseffectwasmimickedby an EP2agonistandmodulatedbyanEP4antagonist. In theairwaysofCOPDsubjects, fibroblast-derivedPGE2 may regulateangiogenesisandinflammation through theproductionofVEGFandIL-8respectively,suggestingthattheincreaseinexpressionofCOX- 2, EP2andEP4observedinCOPD fibroblasts maycontributetosteeringtheroleofPGE2 from homeo- static topro-inflammatory