title: Interferon-gamma expression by intraepithelial lymphocytes results in a loss of epithelial barrier function in a mouse model of total parenteral nutrition.
abstract: OBJECTIVE
  To determine the etiology of the loss of epithelial barrier function observed with the administration of total parenteral nutrition (TPN) in a mouse model.
  
  
  BACKGROUND
  Removal of enteral nutrition with the administration of TPN is associated with a loss of intestinal epithelial barrier function. The etiology of this barrier loss is not clear. Because intraepithelial lymphocytes (IELs) produce a number of cytokines that may alter epithelial permeability, the authors investigated IEL cytokine expression in a mouse model of TPN.
  
  
  METHODS
  Adult C57BL/6 mice received TPN or enteral diet for 7 days. IELs were subsequently harvested and the mRNA expression of cytokines was measured. Epithelial barrier function was assessed in vitro with 51Cr-EDTA in Ussing chambers and was expressed as the permeability coefficient (Papp).
  
  
  RESULTS
  IEL mRNA expression of interferon-gamma (IFN-gamma) rose from 0.14 +/- 0.07 in the control (enterally fed) group to 0.44 +/- 0.11 attomoles/microL in the TPN group (P <.05). Transforming growth factor-beta1 declined slightly but not significantly, from 0.75 +/- 0.35 to 0.55 +/- 0.18 attomoles/microL in the control and TPN groups, respectively. Epithelial barrier function declined significantly with TPN compared to controls. To assess the relevance of IFN-gamma changes, permeability in IFN-gamma knockout mice was studied. Barrier function was significantly higher in IFN-gamma knockout mice on TPN compared to C57BL/6 mice that received TPN.
  
  
  CONCLUSIONS
  IEL cytokine expression changes significantly with TPN administration. The partial correction with IFN-gamma knockout mice suggests that an upregulation of IFN-gamma expression is one mechanism responsible for the loss of the epithelial barrier associated with TPN.
authors.affiliation: Section of Pediatric Surgery, The University of Michigan Medical School and C. S. Mott Children's Hospital, Ann Arbor, Michigan, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Irfan
authors.initials: I
authors.lastname: Kiristioglu
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Fan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Forbush
authors.forename: D Keith
authors.initials: DK
authors.lastname: Bishop
authors.forename: Paul A
authors.initials: PA
authors.lastname: Antony
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000096:biosynthesis*; D007410:Intestinal Diseases / Q000209:etiology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
chemical_list: C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma