Document Detail


INHIBITION OF NF-κB SENSITISES ANTERIOR PITUITARY CELLS TO TNF-α- AND LPS-INDUCED APOPTOSIS.
MedLine Citation:
PMID:  21564349     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
NF-κB, an important proinflammatory factor, is a crucial regulator of cell survival. Both lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) activate NF-κB signalling. Oestrogens were shown to suppress NF-κB activation. Oestrogens exert a sensitizing action to proapoptotic stimuli such as LPS and TNF-α in anterior pituitary cells. In the present study, we show by Western blot that 17β-oestradiol (E(2) ) decreases TNF-α-induced NF-κB/p65 and p50 nuclear translocation in primary cultures of anterior pituitary cells from ovariectomized (OVX) rats. Also, 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 proapoptotic 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 TUNEL assay. 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 FACS). Also, 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 sensitised anterior pituitary cells to the proapoptotic action of LPS and TNF-α. Since 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:
Guadalupe Eijo; Sandra Zárate; Gabriela Jaita; Jimena Ferraris; María Laura Magri; Verónica Zaldivar; Daniela Radl; Valeria Boti; Daniel Pisera; Adriana Seilicovich
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-12
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  -     ISSN:  1365-2826     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Journal of Neuroendocrinology © 2011 Blackwell Publishing.
Affiliation:
Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires (ABG1121), Argentina.
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