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

Tumor necrosis factor α, an early embryonic product, modulates endometrial epithelial cell migration and expression of milk fat globule–epidermal growth factor 8 protein (MFG-E8).

Like Comment


Liang Yu, Ph.D., Sandra Anderson, B.S., Sergio Oehninger, M.D., Ph.D., Silvina Maria Bocca, M.D., Ph.D., H.C.L.D.

Volume 101, Issue 2, Pages 552-559, February 2014



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.


In vitro study.


Academic center.


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.


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.


TNF-α up-regulates endometrial epithelial cell migration and MFG-E8 production, which are critical steps required for the endometrial changes during menstrual cycle as well as during embryonic attachment and invasion.

Read the full text at: http://www.fertstert.org/article/S0015-0282(13)03195-6/fulltext

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.