CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Hexachlorobenzene exposure enhances COX-2 expression and metalloprotease activities in human endometrial stromal cells
Autor/es:
CHIAPPINI, FLORENCIA; BASTON, JUAN IGNACIO; VACCAREZZA, AGUSTINA; SINGLA, JOSÉ; PONTILLO, CAROLINA; MIRET, NOELA; FARINA, MARIANA; MERESMAN, GABRIELA; RANDI, ANDREA
Lugar:
Edinburgo, Escocia
Reunión:
Congreso; 50th Congress of the European Societies of Toxicology EUROTOX; 2014
Institución organizadora:
European Societies of Toxicology EUROTOX
Resumen:
Hexachlorobenzene exposure enhances COX-2 expression and metalloprotease activities in human endometrial stromal cells FA Chiappini1,5, JI Bastón2, A Vaccarezza3,JJ Singla4, CA Pontillo1, N Miret1, M Farina5, G Meresman2, AS Randi1 (1)Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Depto de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. (2)Laboratorio de Fisiopatología Endometrial, Instituto de Biología y Medicina Experimental, IBYME-CONICET, Buenos Aires, Argentina; (3)CEBBAD, Universidad Maimónides, Buenos Aires, Argentina; (4) Servicio de Ginecología, Hospital de Clínicas ?José de San Martín?; (5)Laboratorio de Fisiopatología Placentaria, CEFYBO, CONICET-UBA, Buenos Aires, Argentina. Endometriosis is a gynecologic disorder characterized by the presence and growth of endometrial tissue in ectopic sites, causing infertility in reproductive-aged women. Evidence has emerged regarding the relation between organochlorine pollutants and endometriosis. Hexachlorobenzene (HCB) is a widely distributed pesticide that induces toxic reproductive effects and is an endocrine disruptor. Cyclooxygenase-2 (COX-2) is involved in pathogenesis of endometriosis. Its inhibition suppresses activity of metalloproteases (MMPs), decreasing invasion of human endometriotic epithelial and stromal cells. Altered patterns of MMPs have been reported in endometrial tissues from patients with endometriosis, suggesting that MMPs play critical roles in endometriosis development. In the present study, we examined the HCB action on MMP2 and MMP9 expression and activities, and COX-2 protein levels in HUF cells, T-HESC cells, and human endometrial stromal primary cultures. Cells were exposure to HCB (0.005, 0.05, 0.5 and 5 µM) during 3 and 24 hs, and protein levels were analyzed by Western Blotting, and MMPs activities by gel zymography. In HUF and T-HESC cells, HCB 0.5 µM increases: a)MMP9 activity (80%,p<0.01), MMP9 expression (53%,p<0.05) and MMP2 activity (53%,p<0.05) at 24 hs; b)COX-2 levels (125%,p<0.05) at 3 hs. In control human endometrial stromal primary cultures, HCB 0.05 µM enhances: a)MMP9-MMP2 activities (100,145%,p<0.05) and expression (690,191%,p<0.01); b)COX-2 levels (303%,p<0.05). However, the pesticide has a lower effect in endometriotic primary cultures, showing a moderate increase in MMP9 and MMP2 expression and activities. In conclusion, our results shown that HCB could contribute to endometriosis development, affecting inflammation and invasion parameters of human endometrial cells.