Submitted on August 19, 2007
Accepted on November 5, 2007
Decline in Intestinal Mucosal IL-10 Expression and Decreased Intestinal Barrier Function in a Mouse Model of Total Parenteral Nutrition
Xiaoyi Sun1, Hua Yang2, Keisuke Nose3, Satoko Nose3, Emir Q Haxhija4, Hiroyuki Koga3, and Daniel H. Teitelbaum5*
1 Department of Surgery, University of Michigan, Ann Arbor, Michigan, United States
2 Surgery, Xinqiao Hospital, Chongqing, Michigan, China
3 Surgery, University of Michigan, Ann Arbor, Michigan, United States; Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, United States
4 Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, United States; Surgery, University of Michigan, Ann Arbor, Michigan, United States
5 Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, United States
* To whom correspondence should be addressed. E-mail: dttlbm{at}umich.edu.
Objective: Loss of intestinal epithelial barrier function is a major problem associated with total parenteral nutrition (TPN) administration. We have previously identified intestinal intraepithelial lymphocyte (IEL)-derived interferon gamma (IFN-
) as a contributing factor to this barrier loss. The objective was to determine whether other IEL-derived cytokines may also contribute to intestinal epithelial barrier breakdown.
Methods: C57BL/6J male mice received TPN or enteral nutrition (control) for 7 days. IEL-derived IL-10 was then measured. A significant decline in IEL-derived interleukin-10 (IL-10) expression was seen with TPN administration, a cytokine that has been shown in vitro to maintain tight junction integrity. We hypothesized that this change in IEL derived IL-10 expression could contribute to TPN-associated barrier loss. An additional group of mice was given exogenous recombinant IL-10
Results: Ussing chamber experiments showed that epithelial barrier function markedly declined in the TPN group. TPN resulted in a significant decrease of IEL-derived IL-10 expression. The expression of several tight junction molecules also decreased with TPN administration. Exogenous IL-10 administration in TPN mice significantly attenuated the TPN-associated the decline in ZO-1, E-cadherin, and Occludin expression, as well as a loss of intestinal barrier function.
Conclusions: TPN administration led to a marked decline in IEL-derived IL-10 expression. This decline was coincident with a loss of intestinal epithelial barrier function. As the decline was partially attenuated with the administration of exogenous IL-10, out findings suggest that loss of IL-10 may be a contributing mechanism to TPN-associated epithelial barrier loss.
