title: Prostaglandin E₂ possesses different potencies in inducing Vascular Endothelial Growth Factor and Interleukin-8 production in COPD human lung fibroblasts.
abstract: 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 from Control (C) (n=6), Smoker (HS) (n=6) and COPD patients (n=8) were cultured, and basal PGE2, VEGF, and IL-8 measured in supernatants by ELISA. COX-1/COX-2 and EP receptors expression were assessed by western blot and by RT-PCR. Release of VEGF and IL-8 by human fetal lung fibroblasts (HFL-1; lung, diploid, human) was evaluated under different conditions. PGE2, VEGF, and IL-8 levels, COX-2, EP2, and EP4 protein expression and mRNA were increased in COPD when compared to Controls. Low concentrations of synthetic PGE2 increased the release of VEGF in HFL-1, but higher concentrations were needed to induce the release of IL-8. This effect was mimicked by an EP2 agonist and modulated by an EP4 antagonist. In the airways of COPD subjects, fibroblast-derived PGE2 may regulate angiogenesis and inflammation through the production of VEGF and IL-8 respectively, suggesting that the increase in expression of COX-2, EP2 and EP4 observed in COPD fibroblasts may contribute to steering the role of PGE2 from homeostatic to pro-inflammatory.
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bonanno
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Giusy Daniela
authors.initials: GD
authors.lastname: Albano
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Liboria
authors.initials: L
authors.lastname: Siena
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Angela Marina
authors.initials: AM
authors.lastname: Montalbano
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Riccobono
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Anzalone
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Chiappara
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Gagliardo
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Profita
authors.affiliation: Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), Palermo, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. Electronic address: angelo.sala@unimi.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sala
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: Angiogenesis; COPD; Cyclooxygenase-2; EP receptors; Lung inflammation; Prostaglandin E(2)