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

Objective(s): To determine whether nuclear factor-kappa B (NF-kappa B) is constitutively and tumor necrosis factor (TNF)-dependently activated in endometriotic cells, whether trichostatin A (TSA) can suppress NF-kappa B 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-kappa B activation and possible suppression by TSA. Western blot analysis was used to determine whether TSA suppresses phosphorylation of I kappa B alpha, phosphorylation of p65 in the cytoplasm and nuclear translocation, and the expression of TRAF2/6 and TAK1. Results: NF-kappa B was constitutively activated in endometriotic cells, but only minimally in endometrial cells. TNF alpha stimulation activated NF-kappa B through induction of I kappa B 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-kappa B activation may play a critical role in the pathogenesis in endometriosis. Targeting NF-kappa B with histone deacetylase inhibitors or other compounds might hold promise as novel therapeutics for endometriosis. Copyright (C) 2010 S. Karger AG, Basel