BACKGROUND: Total parenteral nutrition (TPN) increases the risk of severe infectious complications such as septic shock, which are believed to be the result of a breakdown of intestinal barrier function and subsequent bacterial translocation. Toll-like receptors (TLRs) comprise a family of membrane proteins that serve as pattern recognition receptors for a variety of microbe-derived molecules and stimulate innate immune responses to microbes. Alteration of intraepithelial lymphocytes (IELs) to TPN administration has been studied extensively. However, few studies have examined the effect of TPN administration on intestinal TLRs. We hypothesized that the expressions of intestinal TLRs and cytokines may change with TPN administration and a lack of enteral feeding. MATERIALS AND METHODS: TPN-treated mice and sham operation mice (control) were killed at 10 days after operation. mRNA expression of intestinal cytokines and TLRs were analyzed with reverse transcription-polymerase chain reaction (RT-PCR) methods. Change in IEL populations was analyzed with flow cytometry. RESULTS: RT-PCR showed varying expression levels of TLRs at different sites on the small intestine and colon. TLR4, TLR5, TLR7, and TLR9 mRNAs were up-regulated in response to TPN administration, particularly in the distal small intestine. CONCLUSIONS: Up-regulation of TLRs in intestine in response to TPN administration and a lack of enteral nutrition may be associated with an increased risk of septic shock due to bacterial translocation caused by Interferon gamma-mediated intestinal epithelial cell apoptosis. Copyright (c) 2010 Elsevier Inc. All rights reserved.
BACKGROUND: Total parenteral nutrition (TPN) increases the risk of severe infectious complications such as septic shock, which are believed to be the result of a breakdown of intestinal barrier function and subsequent bacterial translocation. Toll-like receptors (TLRs) comprise a family of membrane proteins that serve as pattern recognition receptors for a variety of microbe-derived molecules and stimulate innate immune responses to microbes. Alteration of intraepithelial lymphocytes (IELs) to TPN administration has been studied extensively. However, few studies have examined the effect of TPN administration on intestinal TLRs. We hypothesized that the expressions of intestinal TLRs and cytokines may change with TPN administration and a lack of enteral feeding. MATERIALS AND METHODS: TPN-treated mice and sham operation mice (control) were killed at 10 days after operation. mRNA expression of intestinal cytokines and TLRs were analyzed with reverse transcription-polymerase chain reaction (RT-PCR) methods. Change in IEL populations was analyzed with flow cytometry. RESULTS: RT-PCR showed varying expression levels of TLRs at different sites on the small intestine and colon. TLR4, TLR5, TLR7, and TLR9 mRNAs were up-regulated in response to TPN administration, particularly in the distal small intestine. CONCLUSIONS: Up-regulation of TLRs in intestine in response to TPN administration and a lack of enteral nutrition may be associated with an increased risk of septic shock due to bacterial translocation caused by Interferon gamma-mediated intestinal epithelial cell apoptosis. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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