title: Expression of autocrine prolactin and the short isoform of prolactin receptor are associated with inflammatory response and apoptosis in monocytes stimulated with Mycobacterium bovis proteins.
abstract: Increased levels of prolactin (PRL) have recently been associated with carcinogenesis and the exacerbation of autoimmune diseases, and might be involved in the progression of tuberculosis (TB). To investigate the relationship between PRL and prolactin receptor (PRLr) expression with inflammatory response and apoptosis in monocytes, we used THP-1 cells stimulated with antigens of the Mycobacterium bovis AN5 strain culture filtrate protein (CFP-M. bovis). Western blot (WB), real-time Polymerase chain reaction (PCR), and immunocytochemistry were performed to identify both PRL and PRLr molecules. PRL bioactivity and proinflammatory cytokine detection were assessed. The results showed that PRL and PRLr messenger RNA (mRNA) were synthesized in THP-1 monocytes induced with CFP-M. bovis at peaks of 176- and 404-fold, respectively. PRL forms of 60 and 80kDa and PRLr isoforms of 40, 50, and 65kDa were also identified as time-dependent, while 60-kDa PRL, as well as 40-, and 50-kDa PRLr, were found as soluble forms in culture media and later in the nucleus of THP-1 monocytes. PRL of 60kDa released by monocytes exhibited bioactivity in Nb2 cells, and both synthesized PRL and synthesized PRLr were related with nitrite and proinflammatory cytokine levels proapoptotic activity in CFP-M. bovis-induced monocytes. Our results suggest the overexpression of a full-autocrine loop of PRL and PRLr in monocytes that enhances the inflammatory response and apoptosis after priming with M. bovis antigens.
authors: Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A.C. (CIATEJ), Guadalajara, Mexico; Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico; Departamento de Investigación y Desarrollo, Laboratorios Virbac América Latina, Guadalajara, Jalisco, Mexico. Electronic address: gonzo_lop82@msn.com.
authors: Gonzalo
authors: G
authors: López-Rincón
authors: Instituto de Investigaciones Biomédicas (IIB), UNAM, Mexico City, Mexico. Electronic address: mancilla@biomedicas.unam.mx.
authors: Raúl
authors: R
authors: Mancilla
authors: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Jalisco, Mexico. Electronic address: analauraps@hotmail.com.
authors: Ana L
authors: AL
authors: Pereira-Suárez
authors: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UdeG), Jalisco, Mexico. Electronic address: nmap_3000@hotmail.com.
authors: Priscila A
authors: PA
authors: Martínez-Neri
authors: Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Tarímbaro, Mexico. Electronic address: ochoaz@umich.mx.
authors: Alejandra
authors: A
authors: Ochoa-Zarzosa
authors: Instituto de Investigación en Ciencias Biomédicas (IICB), CUCS, UdeG, Jalisco, Mexico. Electronic address: biologiamolecular@hotmail.com.
authors: José Francisco
authors: JF
authors: Muñoz-Valle
authors: Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A.C. (CIATEJ), Guadalajara, Mexico. Electronic address: cestrada.ciatej@gmail.com.
authors: Ciro
authors: C
authors: Estrada-Chávez
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009163:Mycobacterium bovis / Q000276:immunology*; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D020033:Protein Isoforms; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D011388:Prolactin
keywords: CFP-Mycobacterium bovis; Isoforms; Monocytes; Prolactin; Prolactin receptor