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EVOKES ENTEROCYTE APOPTOSIS WITH PARENTERAL NUTRITION IN MICE
1 The Department of Surgery, The Section of Pediatric Surgery, The University of Michigan, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: dttlbm{at}umich.edu.
Total parenteral nutrition (TPN) results in an increase in intraepithelial lymphocyte (IEL)-derived interferon gamma (IFN-
) expression as well as an increase in epithelial cell apoptosis. This study examined the role that IEL-derived IFN- has in the increase in epithelial cell (EC) apoptosis. Mice received either TPN or oral feedings for 7 days. Small bowel EC apoptosis significantly rose in mice receiving TPN. Administration of TPN also significantly increased IEL-derived IFN- and FasL expression. EC apoptosis in IFN- knockout mice (IFNKO) 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 wild-type TPN mice. Apoptosis in lpr (Fas deficient) and gld (FasL deficient) mice that received TPN was significantly lower than in wild-type mice that received TPN. The TPN-induced increase in IFN- 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.
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