Peritonitis activates transcription of the human prolactin locus in myeloid cells in a humanized transgenic rat model

Sabrina Semprini, Anne V McNamara, Raheela Awais, Karen Featherstone, Claire V Harper, Judith R McNeilly, Amanda Patist, Adriano G Rossi, Ian Dransfield, Alan S McNeilly, Julian R E Davis, Michael R H White, John J Mullins

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2724-34
Number of pages11
JournalEndocrinology
Volume153
Issue number6
Early online date1 Jun 2012
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Animals
  • Bone Marrow Cells/metabolism
  • CD11b Antigen/metabolism
  • Cells, Cultured
  • Gene Expression/drug effects
  • Humans
  • Lipopolysaccharides/pharmacology
  • Luciferases/genetics
  • Macrophages/metabolism
  • Microscopy, Fluorescence
  • Monocytes/metabolism
  • Myeloid Cells/metabolism
  • Neutrophils/metabolism
  • Peritonitis/chemically induced
  • Prolactin/genetics
  • Rats
  • Rats, Transgenic
  • Regulatory Sequences, Nucleic Acid/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thioglycolates/pharmacology
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha/pharmacology

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