title: 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.
abstract: 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.
  
  
  METHODS
  In vitro study.
  
  
  METHODS
  Academic center.
  
  
  METHODS
  Ishikawa cells, used as surrogates for human epithelial cells, were treated with and without TNF-α.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Anderson
authors.affiliation: Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Sergio
authors.initials: S
authors.lastname: Oehninger
authors.affiliation: Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia. Electronic address: boccaS@evms.edu.
authors.forename: Silvina
authors.initials: S
authors.lastname: Bocca
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D008894:Milk Proteins / Q000096:biosynthesis*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
keywords: Human endometrium; MFG-E8; TNF-α; cell migration