title: Peritonitis activates transcription of the human prolactin locus in myeloid cells in a humanized transgenic rat model.
abstract: Prolactin (PRL) is mainly expressed in the pituitary in rodents, whereas in humans, expression is observed in many extrapituitary sites, including lymphocytes. Due to the lack of adequate experimental models, the function of locally produced PRL in the immune system is largely unknown. Using transgenic rats that express luciferase under the control of extensive human PRL regulatory regions, we characterized immune cell responses to thioglycollate (TG)-induced peritonitis. Resident populations of myeloid cells in the peritoneal cavity of untreated rats expressed barely detectable levels of luciferase. In contrast, during TG-induced peritonitis, cell-specific expression in both neutrophils and monocytes/macrophages in peritoneal exudates increased dramatically. Elevated luciferase expression was also detectable in peripheral blood and bone marrow CD11b(+) cells. Ex vivo stimulation of primary myeloid cells showed activation of the human extrapituitary promoter by TNF-α, lipopolysaccharide, or TG. These findings were confirmed in human peripheral blood monocytes, showing that the transgenic rat provided a faithful model for the human gene. Thus, the resolution of an inflammatory response is associated with dramatic activation of the PRL gene promoter in the myeloid lineage.
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom. sabrina.semprini@ed.ac.uk
authors.forename: Sabrina
authors.initials: S
authors.lastname: Semprini
authors.forename: Anne V
authors.initials: AV
authors.lastname: McNamara
authors.forename: Raheela
authors.initials: R
authors.lastname: Awais
authors.forename: Karen
authors.initials: K
authors.lastname: Featherstone
authors.forename: Claire V
authors.initials: CV
authors.lastname: Harper
authors.forename: Judith R
authors.initials: JR
authors.lastname: McNeilly
authors.forename: Amanda
authors.initials: A
authors.lastname: Patist
authors.forename: Adriano G
authors.initials: AG
authors.lastname: Rossi
authors.forename: Ian
authors.initials: I
authors.lastname: Dransfield
authors.forename: Alan S
authors.initials: AS
authors.lastname: McNeilly
authors.forename: Julian R E
authors.initials: JR
authors.lastname: Davis
authors.forename: Michael R H
authors.initials: MR
authors.lastname: White
authors.forename: John J
authors.initials: JJ
authors.lastname: Mullins
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013864:Thioglycolates / Q000494:pharmacology / Q000633:toxicity; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D039481:CD11b Antigen; D008070:Lipopolysaccharides; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D011388:Prolactin; D008156:Luciferases