Intraepithelial lymphocyte-derived interferon-gamma evokes enterocyte apoptosis with parenteral nutrition in mice.
Total parenteral nutrition (TPN) results in an increase in intraepithelial lymphocyte (IEL)-derived interferon-gamma (IFN-gamma) expression as well as an increase in epithelial cell (EC) apoptosis. This study examined the role that IEL-derived IFN-gamma has in the increase in EC apoptosis. Mice received either TPN or oral feedings for 7 days. Small bowel EC apoptosis significantly rose in mice receiving TPN. The administration of TPN also significantly increased IEL-derived IFN-gamma and Fas ligand (FasL) expression. EC apoptosis in IFN-gamma knockout (IFNKO) mice that received TPN was significantly lower than in wild-type TPN mice. Sensitivity of EC to Fas-mediated apoptosis in IFNKO mice was significantly lower than in wild-type TPN mice. Apoptosis in Fas-deficient and FasL-deficient mice that received TPN was significantly lower than in wild-type mice that received TPN. The TPN-induced increase in IFN-gamma expression appears to result in an increase in Fas-L expression and EC sensitivity to Fas, with a resultant increase in EC apoptosis. This may well be one of the mediators of increased EC apoptosis observed with TPN administration.
Yang
Hua
H
Section of Pediatric Surgery, Department of Surgery, University of Michigan Medical School and C. S. Mott Children's Hospital, Ann Arbor, Michigan 48109, USA.
Fan
Yongyi
Y
Teitelbaum
Daniel H
DH
D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D020895:Enterocytes / Q000276:immunology / Q000473:pathology; D053222:Fas Ligand Protein; D015870:Gene Expression / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010288:Parenteral Nutrition / Q000009:adverse effects*; D013047:Specific Pathogen-Free Organisms; D019014:fas Receptor / Q000378:metabolism
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor; D007371:Interferon-gamma