CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Participation of the endocannabinoid system on the protective effect of progesterone in peripheral blood mononuclear cell.
Autor/es:
MANUEL L. WOLFSON; JULIETA AISEMBERG; CLAUDIA A. VERCELLI; ANA MARÍA FRANCHI
Lugar:
CABA
Reunión:
Congreso; 3rd Latin-american Symposium of Reproductive Immunology 2011.; 2011
Institución organizadora:
Capítulo Latinoamericano (CLA) y Sociedad Americana de Inmunología de la Reproducción.
Resumen:
Endoncannabinoids are an emerging class of lipid
mediators which mimic some of the effects of Tetrahydrocannabinol (THC). A
major endocannabinoid, anandamide (AEA), is necessary for the implantation
process but high levels of this mediator is related to early abortion in women.
Lypopolysaccharide (LPS) induces AEA synthesis
in murine macrophages and also inhibits the activity of the enzyme that
degrades AEA (fatty acid amidohydrolase, FAAH) peripheral blood lymphocytes
from healthy women. Previous studies from our laboratory indicate that LPS
causes embryonic resorption in mice with a decrease in progesterone (P) serum
levels. The aim of this work was to study if P modulates the endocannabinoid system
and which progesterone receptors are involved in this effect in murine
peripheral blood mononuclear cells (PBMC). PBMC from pregnant mice showed higher
FAAH activity than PBMC from non pregnant animals (NP) (p<0.05). LPS
decreases FAAH activity (radioconvertion, p<0.05) , protein level (WB,
p<0.05) and mRNA (PCR, p<0.05) in NP mice and P abrogates the endotoxin
effect (p<0.05). This protective effect of P is abolished with two P
antagonists (RU486 and Lonaprizan) (p<0.05). On the other hand, LPS doesn´t modify
FAAH activity in pregnant mice but if we administrate a P antagonist, such as
RU486, previously to LPS administration, FAAH activity decreases (p<0.05)
suggesting the elevated levels of P during pregnancy block the effect of the
endotoxin. Then, we studied the expression of P receptor (PR) and we not only detected
the expression of both PR, PRA and PRB, but also showed their modulation by LPS
and P. Most of the PBMC are CD3+ (flow cytometry) and CD3+ cells express PR
(flow citometry and immunofluorescense). These results suggest that
progesterone, through their classical receptors, have a protective effect on
inflammatory processes mediated by AEA.