Estrogen Signaling through the G Protein–Coupled Estrogen Receptor Regulates Granulocyte Activation in Fish
| Autor: | Isabel Cabas, M. Carmen Rodenas, E. Abellán, José Meseguer, Victoriano Mulero, Alfonsa García-Ayala |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Granulocyte activation Membrane estrogen receptor Acuicultura Neutrophils Immunology Estrogen receptor CREB Neutrophil Activation Receptors G-Protein-Coupled Internal medicine Cyclic AMP medicine Animals Immunology and Allergy Centro Oceanográfico de Murcia RNA Messenger Phosphorylation Cyclic AMP Response Element-Binding Protein Protein kinase A Cells Cultured biology Estrogens Acquired immune system Cyclic AMP-Dependent Protein Kinases Sea Bream Cell biology Endocrinology Receptors Estrogen Prostaglandin-Endoperoxide Synthases biology.protein Signal transduction GPER Granulocytes Signal Transduction |
| Zdroj: | e-IEO: Repositorio Institucional Digital de Acceso Abierto del Instituto Español de Oceanografía Instituto Español de Oceanografía e-IEO. Repositorio Institucional Digital de Acceso Abierto del Instituto Español de Oceanografía instname |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1301613 |
| Popis: | Neutrophils are major participants in innate host responses. It is well known that estrogens have an immune-modulatory role, and some evidence exists that neutrophil physiology can be altered by these molecules. Traditionally, estrogens act via classical nuclear estrogen receptors, but the identification of a G protein–coupled estrogen receptor (GPER), a membrane estrogen receptor that binds estradiol and other estrogens, has opened up the possibility of exploring additional estrogen-mediated effects. However, information on the importance of GPER for immunity, especially, in neutrophils is scant. In this study, we report that gilthead seabream (Sparus aurata L.) acidophilic granulocytes, which are the functional equivalent of mammalian neutrophils, express GPER at both mRNA and protein levels. By using a GPER selective agonist, G1, it was found that GPER activation in vitro slightly reduced the respiratory burst of acidophilic granulocytes and drastically altered the expression profile of several genes encoding major pro- and anti-inflammatory mediators. In addition, GPER signaling in vivo modulated adaptive immunity. Finally, a cAMP analog mimicked the effects of G1 in the induction of the gene coding for PG-endoperoxide synthase 2 and in the induction of CREB phosphorylation, whereas pharmacological inhibition of protein kinase A superinduced PG-endoperoxide synthase 2. Taken together, our results demonstrate for the first time, to our knowledge, that estrogens are able to modulate vertebrate granulocyte functions through a GPER/cAMP/protein kinase A/CREB signaling pathway and could establish therapeutic targets for several immune disorders in which estrogens play a prominent role. The Journal of Immunology, 2013, 191: 4628–4639. SI |
| Databáze: | OpenAIRE |
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