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Inhibition of nuclear factor-kappa B sensitises anterior pituitary cells to tumour necrosis factor-α- and lipopolysaccharide-induced apoptosis.
J Neuroendocrinol. 2011 Aug; 23(8):651-9.JN

Abstract

Nuclear factor-kappa B (NF-κB), an important pro-inflammatory factor, is a crucial regulator of cell survival. Both lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-α activate NF-κB signalling. Oestrogens were shown to suppress NF-κB activation. Oestrogens exert a sensitising action to pro-apoptotic stimuli such as LPS and TNF-α in anterior pituitary cells. In the present study, we show by western blotting that 17β-oestradiol (E(2)) decreases TNF-α-induced NF-κB/p65 and p50 nuclear translocation in primary cultures of anterior pituitary cells from ovariectomised (OVX) rats. Also, the in vivo administration of E(2) decreases LPS-induced NF-κB/p65 and p50 nuclear translocation. To investigate whether the inhibition of NF-κB pathway sensitises anterior pituitary cells to pro-apoptotic stimuli, we used an inhibitor of NF-κB activity, BAY 11-7082 (BAY). BAY, at a concentration that fails to induce apoptosis, has permissive action on TNF-α-induced apoptosis of lactotrophs and somatotrophs from OVX rats, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Pharmacological inhibition of NF-κB signalling enhances E(2)-sensitising effect to TNF-α-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 E(2) administration. Our results show that inhibition of the NF-κB signalling pathway sensitises anterior pituitary cells to the pro-apoptotic action of LPS and TNF-α. Because E(2) inhibits LPS- and TNF-α-activated NF-κB nuclear translocation, the present study suggests that E(2) sensitises anterior pituitary cells to TNF-α- and LPS-induced apoptosis by inhibiting NF-κB activity.

Authors+Show Affiliations

Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21564349

Citation

Eijo, G, et al. "Inhibition of Nuclear Factor-kappa B Sensitises Anterior Pituitary Cells to Tumour Necrosis Factor-α- and Lipopolysaccharide-induced Apoptosis." Journal of Neuroendocrinology, vol. 23, no. 8, 2011, pp. 651-9.
Eijo G, Zárate S, Jaita G, et al. Inhibition of nuclear factor-kappa B sensitises anterior pituitary cells to tumour necrosis factor-α- and lipopolysaccharide-induced apoptosis. J Neuroendocrinol. 2011;23(8):651-9.
Eijo, G., Zárate, S., Jaita, G., Ferraris, J., Magri, M. L., Zaldivar, V., Radl, D., Boti, V., Pisera, D., & Seilicovich, A. (2011). Inhibition of nuclear factor-kappa B sensitises anterior pituitary cells to tumour necrosis factor-α- and lipopolysaccharide-induced apoptosis. Journal of Neuroendocrinology, 23(8), 651-9. https://doi.org/10.1111/j.1365-2826.2011.02157.x
Eijo G, et al. Inhibition of Nuclear Factor-kappa B Sensitises Anterior Pituitary Cells to Tumour Necrosis Factor-α- and Lipopolysaccharide-induced Apoptosis. J Neuroendocrinol. 2011;23(8):651-9. PubMed PMID: 21564349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of nuclear factor-kappa B sensitises anterior pituitary cells to tumour necrosis factor-α- and lipopolysaccharide-induced apoptosis. AU - Eijo,G, AU - Zárate,S, AU - Jaita,G, AU - Ferraris,J, AU - Magri,M L, AU - Zaldivar,V, AU - Radl,D, AU - Boti,V, AU - Pisera,D, AU - Seilicovich,A, PY - 2011/5/14/entrez PY - 2011/5/14/pubmed PY - 2011/12/14/medline SP - 651 EP - 9 JF - Journal of neuroendocrinology JO - J Neuroendocrinol VL - 23 IS - 8 N2 - Nuclear factor-kappa B (NF-κB), an important pro-inflammatory factor, is a crucial regulator of cell survival. Both lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-α activate NF-κB signalling. Oestrogens were shown to suppress NF-κB activation. Oestrogens exert a sensitising action to pro-apoptotic stimuli such as LPS and TNF-α in anterior pituitary cells. In the present study, we show by western blotting that 17β-oestradiol (E(2)) decreases TNF-α-induced NF-κB/p65 and p50 nuclear translocation in primary cultures of anterior pituitary cells from ovariectomised (OVX) rats. Also, the in vivo administration of E(2) decreases LPS-induced NF-κB/p65 and p50 nuclear translocation. To investigate whether the inhibition of NF-κB pathway sensitises anterior pituitary cells to pro-apoptotic stimuli, we used an inhibitor of NF-κB activity, BAY 11-7082 (BAY). BAY, at a concentration that fails to induce apoptosis, has permissive action on TNF-α-induced apoptosis of lactotrophs and somatotrophs from OVX rats, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Pharmacological inhibition of NF-κB signalling enhances E(2)-sensitising effect to TNF-α-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 E(2) administration. Our results show that inhibition of the NF-κB signalling pathway sensitises anterior pituitary cells to the pro-apoptotic action of LPS and TNF-α. Because E(2) inhibits LPS- and TNF-α-activated NF-κB nuclear translocation, the present study suggests that E(2) sensitises anterior pituitary cells to TNF-α- and LPS-induced apoptosis by inhibiting NF-κB activity. SN - 1365-2826 UR - https://www.unboundmedicine.com/medline/citation/21564349/Inhibition_of_nuclear_factor_kappa_B_sensitises_anterior_pituitary_cells_to_tumour_necrosis_factor_α__and_lipopolysaccharide_induced_apoptosis_ L2 - https://doi.org/10.1111/j.1365-2826.2011.02157.x DB - PRIME DP - Unbound Medicine ER -