title: The pivotal role of tumor necrosis factor-alpha in signaling apoptosis in intestinal epithelial cells under shock conditions.
abstract: BACKGROUND
  Apoptosis is essential for the regulation of cell number and function of intestinal epithelial cells but may contribute to intestinal barrier failure after shock and other low-flow conditions to the gut.
  
  
  METHODS
  Caco2 intestinal cell monolayers were challenged with recombinant tumor necrosis factor (TNF). In a second group of experiments, Caco2 cells were exposed to bacteria and/or hypoxia followed by reoxygenation. Apoptosis was detected using annexin-V propidium-iodide staining. Cell culture supernatants were also obtained in the second group of experiments and TNF levels quantitated. Monolayer integrity was assessed by measurement of paracellular permeability and transepithelial electrical resistance.
  
  
  RESULTS
  Apical but not basal recombinant TNF increased Caco2 apoptosis. Exposure to either bacteria alone or hypoxia/reoxygenation alone did not increase apoptosis; however, the combined insults significantly increased apoptosis. The increased apoptosis occurred in a delayed fashion in both groups. TNF was released in a polar fashion, and the greatest levels were noted after exposure to both bacteria and hypoxia-reoxygenation. There was also an increase in paracellular permeability in this group; however, no change in transepithelial electrical resistance was noted. The effects on apoptosis and permeability were abrogated by anti-TNF antibodies.
  
  
  CONCLUSIONS
  Intestinal epithelial cell apoptosis contributes to barrier failure after shock conditions and is related to augmented TNF release.
authors.affiliation: Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. idiebel@med.wayne.edu
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Diebel
authors.forename: David M
authors.initials: DM
authors.lastname: Liberati
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Baylor
authors.forename: William J
authors.initials: WJ
authors.lastname: Brown
authors.forename: Clement A
authors.initials: CA
authors.lastname: Diglio
mesh_terms: D017209:Apoptosis; D018938:Caco-2 Cells; D002478:Cells, Cultured; D004927:Escherichia coli Infections / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D012769:Shock / Q000378:metabolism* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha