Esta web utiliza cookies. Si continúas navegando consideramos que aceptas su uso.
Más información
Aceptar
I Jornadas Científicas del IMIB-Arrixaca
Acceso Personal
Contacto
Aviso Legal
Inicio
Bienvenida
Comités
Ponencias
Comunicaciones
Programa
Fechas clave
Inscripciones
Selección comunicaciones
Enviar comunicación
Patrocinadores
Sede
Imprimir
GPER1 REGULATES HUMAN NEUTROPHIL FUNCTIONS
Autores:
MARÍA DEL CARMEN RODENAS BLEDA
, NICOLA TAMASSIA,
ISABEL CABAS SÁNCHEZ
, FEDERICA CALZETTI,
JOSE MESEGUER PEÑALVER
, MARCO A. CASSATELLA,
ALFONSA GARCÍA AYALA
,
VICTORIANO MULERO MÉNDEZ
,
Grupos de investigación:
[GI/IMIB/C060/2011] Inmunidad, inflamación y cáncer
Comunicación:
Antecedentes:
The role of estrogens in immune functioning is relatively well known under both physiological and pathological conditions. Thus, these sex steroids have been identified as being responsible for the sexual dimorphism observed in some chronic inflammatory and autoimmune diseases. Neutrophils are the most abundant circulating leukocytes in humans, and their abundance and function are regulated by estrogens since they express estrogen receptors (ERs). Traditionally, estrogens were thought to act via classical nuclear ERs, namely ER? and ER?. However, it was observed that some estrogens induced biological effects only minutes after their application. This rapid, “non-genomic” effect of estrogens is mediated by a membrane anchored receptor called G protein-coupled estrogen receptor 1 (GPER1). Nevertheless, the expression and role of GPER1 in the immune system has not been exhaustively studied and its relevance in neutrophil functions remains unknown. Using G1, a GPER1-selective ligand, we recently reported that gilthead seabream (Sparus aurata L., Teleostei) acidophilic granulocytes, which are the functional equivalent of mammalian neutrophils, express a functional GPER1 which regulates their main functional activities through a cAMP/protein kinase A/CREB signaling pathway.
Métodos:
Neutrophils were isolated under endotoxin-free conditions from buffy coats of healthy donors after centrifugation over Ficoll-Paque, followed by dextran sedimentation and hypotonic lysis of contaminating erythrocytes. To analize gen expression we used reverse transcription quantitative real-time PCR (RT-qPCR). For phenotypic studies we used flow cytometry analysis. Western blotting to determine signaling pathway. Detection of cytokine release by ELISA. The respiratory burst was analize by superoxide anion (O2-) release was estimated by the cytochrome C reduction. Statistical evaluation was performed using one-way ANOVA followed by Tukey’s post hoc test.
Resultados:
In the present study, we show that human neutrophils also express a functional GPER1 which regulates their functions through the same signaling pathway. Thus, GPER1 activation in vitro increases respiratory burst of neutrophils, extends their life span and drastically alters their gene expression pro?le.
Conclusiones:
Collectively, our results demonstrate that GPER1 activation promotes the polarization of human neutrophils towards a pro-inflammatory phenotype. It is evident, then, that the regulation of neutrophil functions by estrogens through GPER1 predates the split of fish and tetrapods more than 450 million years ago, and points to GPER1 as a potential therapeutic target in immune diseases where neutrophils play a key role.
Instituto de Investigación Sanitaria Acreditado
Inicio
Grupo de Investigación
Miembros
Proyectos
Colaboraciones
Servicios
Recursos formativos
Producción Científica
Publicaciones
Tesis
Novedades
Noticias
Eventos
Convocatorias
Agenda