Tumor necrosis factor α up-regulates endometrial milk fat globule-epidermal growth factor 8 protein production via nuclear factor κB activation, resulting in cell migration of epithelial cells

肿瘤坏死因子α通过核因子κB激活上调子宫内膜乳脂肪球-表皮生长因子8蛋白质的产生,导致上皮细胞的细胞迁移

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作者:Liang Yu, Sandra Anderson, Sergio Oehninger, Silvina Bocca

Objective

To explore the role of tumor necrosis factor (TNF) α, an early embryonic product, on endometrial epithelial cell migration and endometrial milk fat globule-epidermal growth factor 8 protein (MFG-E8) production. Design: In vitro study. Setting: Academic center. Intervention(s): Ishikawa cells, used as surrogates for human epithelial cells, were treated with and without TNF-α. Main outcome measure(s): Effect of TNF-α on intracellular MFG-E8 protein was evaluated with the use of ELISA, Western blot, and subcellular fractionation. Specific inhibitors were used to study TNF-α mechanism of action. Effect of TNF-α on cell migration was studied with the use of a wound healing assay and reorganization of E-cadherin. Result(s): TNF-α induced: 1) significant up-regulation of MFG-E8 intracellular protein, which was attenuated by pretreatment with a specific inhibitor of nuclear factor κB; 2) increased transcription of MFG-E8 and other proinflammatory factors, such as interleukins 6 and 8, which were suppressed by cotreatment with hCG; and 3) significant cell migration with E-cadherin remodeling, changes associated with subcellular MFG-E8 relocalization.

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