title: Prolactin modulates cytokine production induced by culture filtrate proteins of M. bovis through different signaling mechanisms in THP1 cells.
abstract: The immunomodulatory functions of prolactin (PRL) are well recognized. Augmented PRL plasma levels were observed in patients with advanced tuberculosis (TB). Recently, we have reported that LPS and Mycobacterium bovis (M. bovis) induced differential expression of PRL receptor (PRLR) isoforms in THP-1 cells and bovine macrophages, respectively. The aim of this work was to determine whether PRL should be considered as a potential modulator of the signaling pathways and cytokine synthesis, induced by culture filtrate protein (CFP) from M. bovis in THP-1 monocytes. The THP-1 cells were stimulated with PRL (20ng/mL), M. bovis CFP (50μg/mL). PRLR as well as phosphorylated STAT3, STAT5, Akt1/2/3, ERK1/2 and p38 expression were evaluated by Western blot. IL1-β, TNF-α, IL-6, IL-12, IL-8, and IL-10 concentrations were measured by ELISA. Our results demonstrated that the expression pattern of PRLR short isoforms is induced by M. bovis CFP. M bovis CFP induced phosphorylation of Akt2, ERK1/2, p38, STAT3, and STAT5 pathways. In turn, PRL only activated the JAK2/STAT3-5 signaling pathway. However, when combined both stimuli, PRL significantly increased STAT3-5 phosphorylation and downregulated Akt2, ERK1/2, and p38 phosphorylation. As expected, M. bovis CFP induced substantial amounts of IL1-β, IL-6, TNF-α, IL-8, IL-12, and IL-10. However, the PRL costimulation considerably decreased IL1-β, TNF-α, and IL-12 secretion, and increased IL-10 production. This results suggest that up-regulation of IL-10 by PRL might be modulating the pro-inflammatory response against mycobacterial antigens through the MAPK pathway.
authors.affiliation: Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico; Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco 44340, Mexico.
authors.forename: Priscila A
authors.initials: PA
authors.lastname: Martínez-Neri
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, Mexico.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: López-Rincón
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas UNAM, Mexico City, Mexico.
authors.forename: Raúl
authors.initials: R
authors.lastname: Mancilla-Jiménez
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco 44340, Mexico.
authors.forename: Susana
authors.initials: S
authors.lastname: del Toro-Arreola
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco 44340, Mexico.
authors.forename: Mary
authors.initials: M
authors.lastname: Fafutis-Morris
authors.affiliation: Instituto de Enfermedades Crónico-Degenerativas, Departamento de Biología Molecular y, Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: Miriam Ruth
authors.initials: MR
authors.lastname: Bueno-Topete
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, Mexico.
authors.forename: Ciro
authors.initials: C
authors.lastname: Estrada-Chávez
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco 44340, Mexico. Electronic address: analauraps@hotmail.com.
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Pereira-Suárez
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002417:Cattle; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000235:genetics; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009163:Mycobacterium bovis / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D011388:Prolactin / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D020033:Protein Isoforms / Q000032:analysis; D011981:Receptors, Prolactin / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C508609:IL10 protein, human; D020033:Protein Isoforms; D011981:Receptors, Prolactin; D016753:Interleukin-10; D011388:Prolactin
keywords: Cytokines JAK/STAT; MAPK; Mycobacterium bovis; PI3K/Akt; Prolactin