title: Lipopolysaccharide induces the expression of an autocrine prolactin loop enhancing inflammatory response in monocytes.
abstract: BACKGROUND
  Prolactin from pituitary gland helps maintain homeostasis but it is also released in immune cells where its function is not completely understood. Pleiotropic functions of prolactin (PRL) might be mediated by different isoforms of its receptor (PRLr).
  
  
  METHODS
  The aim of this study was to investigate the relationship between the eventual synthesis of PRL and PRLr isoforms with the inflammatory response in monocytes. We used THP-1 and monocytes isolated from healthy subjects stimulated with lipopolysaccharide (LPS). Western blot, real time PCR and immunocytochemistry were performed to identify both molecules. The bioactivity of the PRL was assessed using a bioassay and ELISA to detect pro inflammatory cytokines.
  
  
  RESULTS
  PRLr mRNA and PRL mRNA were synthesized in THP-1 monocytes activated with LPS with peaks of 300-fold and 130-fold, respectively. The long (100 kDa) and the intermediate (50 kDa) isoforms of PRLr and big PRL (60 kDa) were time-dependent upregulated for monocytes stimulated with LPS. This expression was confirmed in monocytes from healthy subjects. The PRLr intermediate isoform and the big PRL were found soluble in the culture media and later in the nucleus in THP-1 monocytes stimulated with LPS. Big PRL released by monocytes showed bioactivity in Nb2 Cells, and both PRL and PRLr, synthesized by monocytes were related with levels of nitrites and proinflammatory citokines.
  
  
  CONCLUSIONS
  Our results suggest the expression of a full-autocrine loop of PRL enhances the inflammatory response in activated monocytes. This response mediated by big PRL may contribute to the eradication of potential pathogens during innate immune response in monocytes but may also contribute to inflammatory disorders.
authors.affiliation: Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco A,C, Guadalajara, Jalisco 44270, México. cestrada.ciatej@gmail.com.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: López-Rincón
authors.forename: Ana L
authors.initials: AL
authors.lastname: Pereira-Suárez
authors.forename: Susana
authors.initials: S
authors.lastname: Del Toro-Arreola
authors.forename: Pedro E
authors.initials: PE
authors.lastname: Sánchez-Hernández
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ochoa-Zarzosa
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
authors.forename: Ciro
authors.initials: C
authors.lastname: Estrada-Chávez