Gene alteration of intestinal intraepithelial lymphocytes with administration of total parenteral nutrition.
BACKGROUND
Total parenteral nutrition (TPN) is associated with sepsis and loss of immune reactivity. The authors previously have shown that changes in the intestinal mucosal immune system--ie, intraepithelial lymphocytes (IEL)--lead to a loss of epithelial barrier function. This may be a mechanism by which bacteria and toxins endanger individuals receiving TPN. To identify altered IEL gene expression during TPN administration, microarray assays were used.


METHODS
Mice received oral feeding (control) or TPN for 7 days. Small bowel IEL were separated and retained, RNA purified, and microarray assays performed (Affymetrix system, 12,491 genes). Results were expressed as quantile-normalized trimmed-means. Significance equals a greater than 2-fold change (TPN v control), P <.01 (t test) or greater than 3-fold, P <.05.


RESULTS
In the TPN group 88, IEL genes were significantly up regulated and 114 downregulated (v control). Of these genes, 4 were identified to have highest degree of upregulation (FK506-binding protein 5; mannose-binding lectin, metallothionein 1 and 2), 2 were highly downregulated (microsomal epoxide hydrolase 1 and cytochrome P450 1a1). These genes were found to have high potential for immune-modulatory effects.


CONCLUSIONS
The observed alterations in IEL gene expression may have an important role in the altered immune response with TPN and may relate to the increase in sepsis with TPN administration.
Wildhaber
Barbara E
BE
Section of Pediatric Surgery, Department of Surgery, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA.
Yang
Hua
H
Tazuke
Yuko
Y
Teitelbaum
Daniel H
DH
D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018189:Immunomagnetic Separation; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D015854:Up-Regulation / Q000235:genetics