Peritonitis Activates Transcription of the Human Prolactin Locus in Myeloid Cells in a Humanized Transgenic Rat Model

• DOI: 10.1210/en.2011-1926
• Publication Date: 2012-04-12T04:33:57Z
• Authors: 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
• Keywords: Lipopolysaccharides; 0301 basic medicine; CD11b Antigen; Neutrophils; Reverse Transcriptase Polymerase Chain Reaction; Macrophages; Gene Expression; Bone Marrow Cells; Peritonitis; Regulatory Sequences, Nucleic Acid; Monocytes; Prolactin; Rats; 3. Good health; 03 medical and health sciences; Microscopy, Fluorescence; Thioglycolates; Animals; Humans; Myeloid Cells; Rats, Transgenic; Luciferases; Cells, Cultured

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.