Inhibition of NF-kB sensitises anterior pituitary cells to TNF-a- and LPS-induced apoptosis

EIJO G; S. ZARATE; JAITA G; FERRARIS J; MAGRI L; ZALDIVAR V; RADL D; BOTI V; D. PISERA; A. SEILICOVICH

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2011 vol. 23 p. 651 - 659

0953-8194

NF-kB, an important proinflammatory factor, is a crucial regulator of cell survival. Both lipopolysaccharide (LPS) and tumor necrosis factor-a (TNF-a) activate NF-kB signalling. Oestrogens were shown to suppress NF-kB activation. Oestrogens exert a sensitizing action to proapoptotic stimuli such as LPS and TNF-a in anterior pituitary cells. In the present study, we show by Western blot that 17b-oestradiol (E2) decreases TNF-a-induced NF-kB/p65 and p50 nuclear translocation in primary cultures of anterior pituitary cells from ovariectomized (OVX) rats. Also, in vivo administration of E2 decreases LPS-induced NF-kB/p65 and p50 nuclear translocation. To investigate whether the inhibition of NF-kB pathway sensitises anterior pituitary cells to proapoptotic stimuli we used an inhibitor of NF-kB activity, BAY 11-7082 (BAY). BAY, at a concentration that fails to induce apoptosis, has permissive action on TNF-a-induced apoptosis of lactotrophs and somatotrophs from OVX rats, as assessed by TUNEL assay. Pharmacological inhibition of NF-kB signalling enhances E2-sensitising effect to TNF-a-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 FACS). Also, LPS-induced expression of Bcl-xL in pituitaries of OVX rats is decreased by E2 administration. Our results show that inhibition of the NF-kB signalling pathway sensitised anterior pituitary cells to the proapoptotic action of LPS and TNF-a. Since E2 inhibits LPS- and TNF-a-activated NF-kB nuclear translocation, the present study suggests that E2 sensitises anterior pituitary cells to TNF-á- and LPS-induced apoptosis by inhibiting NF-kB activity.