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IMPACT OF THE ENDOCRINE DISRUPTOR 17A-ETHINYLESTRADIOL ON THE IMMUNE RESPONSE
Autores:
NURIA ESTHER GÓMEZ GONZÁLEZ
, ALICIA GARCÍA ALCÁZAR,
MªPILAR SEPULCRE CORTÉS
,
VICTORIANO MULERO MÉNDEZ
,
ALFONSA GARCÍA AYALA
,
Grupos de investigación:
[GI/IMIB/C060/2011] Inmunidad, inflamación y cáncer
Comunicación:
Antecedentes:
17?-ethinylestradiol (EE2), a synthetic estrogen used in most oral contraceptives pills and hormone replacement therapy, is able to modulate the immune responses. The gilthead seabream, Sparus aurata L., is a hermaphrodite marine teleost fish which have a great economic value in the Mediterranean area that is used to study the impact of endocrine disruptors in immunity. In previous studies, we have described that immune cells of adult seabream fish express estrogens receptors (ERs) and that EE2, which has been found widely spread in the water bodies, acts as an endocrine disruptor. Moreover, EE2 alters the capacity of gilthead seabream to appropriately respond to infection. However, those studies are mainly focus on head-kidney leukocytes and no information exists on the effects of EE2 on the gilthead seabream peritoneal exudate cells (PECs).
Métodos:
The aim of this research is to study the effect of EE2 on the innate immune system of seabream focusing on the possible alterations produced in PECs. For this reason, juvenile gilthead seabream specimens were fed three times at day with pellet diet supplemented with EE2 (5 ?g/g food, treated) or unsupplemented (untreated) for 3 months. Moreover, they were intraperitoneally injected with hemocyanin (45 ?g/fish) and Imject Alum adjuvant (3.6 ?g/fish) (vaccinated) or phosphate buffered saline (unvaccinated) the last day of the EE2 treatment (priming) and three months later (booster).
Resultados:
One day after the priming, EE2 increased the number of recruited cells in the PECs and the expression levels of gene encoding markers for macrophages and B and T lymphocytes. Moreover, EE2 augmented the respiratory burst activity and the gene expression level of interleukin 1ß (il1b) PECs. Interestingly, decreased gene expression levels of the histamine receptor 2 (hr2) was found in the treated group. One day after booster, the EE2 treated group showed lower percentage of B lymphocytes, higher expression of the macrophage gene marker and lower respiratory burst activity. Fifty days after booster, leukocyte recruitment and histamine receptor 1 (hr1) expression decreased in treated group while the respiratory burst and the expression of il1b increased, as happened in vaccinated fish. In addition, the vaccinated and EE2 treated group showed lower acidophilic granulocytes and higher B lymphocyte numbers.
Conclusiones:
In conclusion, EE2 alters PEC abundance and recruitment, their respiratory burst and expression of il1b, hr1 and hr2. These results demonstrate the inflammatory effect of EE2 in fish PECs and confirm its modulatory role of innate and acquired immunity. Financial Support: Fundación Séneca Agencia de Ciencia y Tecnología Región de Murcia 19883/GERM/15 and MINECO AGL2014-53167-C3-1-R.
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