title: Prolactin increases HO-1 expression and induces VEGF production in human macrophages.
abstract: The pituitary hormone prolactin (PRL) is a multifunctional polypeptide which exerts a role on cell proliferation and may also contribute to cell differentiation. PRL is also produced by immune cells and is regarded as a key component of the neuroendocrine-immune loop and as a local regulator of macrophage response. The involvement of PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL receptors in these cells. It has been shown that PRL possess both angiogenic and antiangiogenic effects. Recently, we revealed that augmentation of HO-1 activity enhances PRL-mediated angiogenesis in human endothelial cells. Since macrophages are key participants in angiogenesis our objective was to investigate the effect of PRL also in human macrophages. In vitro treatment of macrophages with PRL was found to increase both heme oxygenase-1 (HO-1) expression and protein synthesis in a time and dose dependent manner as quantified respectively by reverse-transcriptase real-time polymerase chain reaction and Western blot analysis. PRL-treated macrophages also showed an enhanced release of vascular endothelial growth factor (VEGF) as demonstrated by ELISA assay. Furthermore, to determine whether PRL-induced HO-1 activity was required for VEGF production by macrophages, the effect of PRL on the induction of VEGF was studied in the presence of an inducer stannic chloride (SnCl(2)) and of an inhibitor stannic mesoporphyrin (SnMP) of HO activity. Our observations suggest that PRL may regulate monocyte activation and influences not only immune function but also angiogenesis.
authors.affiliation: Department of Biomedical Sciences, University of Catania, Italy. lucmal@mbox.unict.it
authors.forename: L
authors.initials: L
authors.lastname: Malaguarnera
authors.forename: R M
authors.initials: RM
authors.lastname: Imbesi
authors.forename: A
authors.initials: A
authors.lastname: Scuto
authors.forename: F
authors.initials: F
authors.lastname: D'Amico
authors.forename: F
authors.initials: F
authors.lastname: Licata
authors.forename: A
authors.initials: A
authors.lastname: Messina
authors.forename: S
authors.initials: S
authors.lastname: Sanfilippo
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism; D017971:Tin Compounds / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D008665:Metalloporphyrins; D017971:Tin Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C055421:tin mesoporphyrin; D013481:Superoxides; C041694:stannic chloride; D011388:Prolactin; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1