Constitutive and Tumor Necrosis Factor-Alpha-Stimulated Activation of Nuclear Factor-KappaB in Immortalized Endometriotic Cells and Their Suppression by Trichostatin A

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This study found that NF-kappaB is constitutively activated in endometriotic cells, and this activation is suppressed by trichostatin A, which also affects p65 phosphorylation and translocation.

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Abstract

OBJECTIVE(S): To determine whether nuclear factor-kappaB (NF-kappaB) is constitutively and tumor necrosis factor (TNF)-dependently activated in endometriotic cells, whether trichostatin A (TSA) can suppress NF-kappaB activation and suppress TRAF2/6 and TAK1, and whether TSA and caffeic acid phenyl ester can suppress constitutive and H(2)O(2)-stimulated proliferation of endometriotic cells. METHODS: Two endometriotic cell lines and an endometrial stromal cell line were used as an in vitro model. Electrophoretic mobility shift analysis was used to determine NF-kappaB activation and possible suppression by TSA. Western blot analysis was used to determine whether TSA suppresses phosphorylation of IkappaBalpha, phosphorylation of p65 in the cytoplasm and nuclear translocation, and the expression of TRAF2/6 and TAK1. RESULTS: NF-kappaB was constitutively activated in endometriotic cells, but only minimally in endometrial cells. TNFalpha stimulation activated NF-kappaB through induction of IkappaB phosphorylation, but the activation can be suppressed by TSA. TSA also attenuated constitutive and TNF-dependent p65 phosphorylation and nuclear translocation in endometriotic cells. TRAF2, TRAF6 and TAK1 were constitutively activated and were unaffected by TSA treatment. CONCLUSIONS: NF-kappaB activation may play a critical role in the pathogenesis in endometriosis. Targeting NF-kappaB with histone deacetylase inhibitors or other compounds might hold promise as novel therapeutics for endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometrium Hydroxamic Acids Stromal Cells TNF Receptor-Associated Factor 2 TNF Receptor-Associated Factor 6 Transcription Factor RelA Caffeic Acids Caffeic Acids Cell Division Cell Division Cell Division Cell Line, Transformed Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Female Histone Deacetylase Inhibitors Histone Deacetylase Inhibitors

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