Inhibition of nuclear factor-kappa B sensitises anterior pituitary cells to tumour necrosis factor-alpha- and lipopolysaccharide-induced apoptosis

EIJO GUADALUPE; ZÁRATE SANDRA; JAITA GABRIELA; FERRARIS JIMENA; MAGRI LAURA; ZALDIVAR VERÓNICA; RADL DANIELA; BOTI VALERIA; PISERA DANIEL; SEILICOVICH ADRIANA

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2011 p. 651 - 659

0953-8194

Nuclear factor-kappa B (NF-êB), an important pro-inflammatory factor, is a crucial regulator of cell survival. Both lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-á activate NF-êB signalling. Oestrogens were shown to suppress NF-êB activation. Oestrogens exert a sensitising action to pro-apoptotic stimuli such as LPS and TNF-á in anterior pituitary cells. In the present study, we show by western blotting that 17â-oestradiol (E2) decreases TNF-á-induced NF-êB/p65 and p50 nuclear translocation in primary cultures of anterior pituitary cells from ovariectomised (OVX) rats. Also, the in vivo administration of E2 decreases LPS-induced NF-êB/p65 and p50 nuclear translocation. To investigate whether the inhibition of NF-êB pathway sensitises anterior pituitary cells to pro-apoptotic stimuli, we used an inhibitor of NF-êB activity, BAY 11-7082 (BAY). BAY, at a concentration that fails to induce apoptosis, has permissive action on TNF-á-induced apoptosis of lactotrophs and somatotrophs from OVX rats, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Pharmacological inhibition of NF-êB signalling enhances E2-sensitising effect to TNF-á-induced apoptosis in lactotrophs but not in somatotrophs. In vivo administration of BAY allowed LPS-induced apoptosis in anterior pituitary cells from OVX rats (determined by fluorescence activated cell sorting). Furthermore, LPS-induced expression of Bcl-xL in pituitaries of OVX rats is decreased by E2 administration. Our results show that inhibition of the NF-êB signalling pathway sensitises anterior pituitary cells to the pro-apoptotic action of LPS and TNF-á. Because E2 inhibits LPS- and TNF-á-activated NF-êB nuclear translocation, the present study suggests that E2 sensitises anterior pituitary cells to TNF-á- and LPS-induced apoptosis by inhibiting NF-êB activity.