Up-Regulation of Intestinal Toll-Like Receptors and Cytokines Expressions Change After TPN Administration and a Lack of Enteral Feeding
Up-Regulation of Intestinal Toll-Like Receptors and Cytokines Expressions Change After TPN Administration and a Lack of Enteral Feeding
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DOI：
10.1016/j.jss.2009.01.022
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发表时间：
2010-05-15
影响因子：
2.2
通讯作者：
Chijiiwa, Kazuo
中科院分区：
文献类型：
--
作者：
Ikeda, Takuto;Hiromatsu, Kenji;Chijiiwa, Kazuo
背景全胃肠外营养（TPN）增加了严重感染性并发症的风险，如脓毒性休克，这被认为是肠道屏障功能破坏和随后细菌移位的结果。Toll样受体（TLR）包括膜蛋白家族，其充当多种微生物衍生分子的模式识别受体并刺激对微生物的先天免疫应答。已经广泛研究了TPN给药后上皮内淋巴细胞（IEL）的变化。然而，很少有研究检查TPN给药对肠道TLR的影响。我们假设肠TLRs和细胞因子的表达可能会随着TPN给药和缺乏肠内喂养而改变。术后10 d处死TPN治疗组和假手术组小鼠。用逆转录-聚合酶链反应（RT-PCR）方法检测肠细胞因子和TLRs的mRNA表达。用流式细胞仪分析IEL群体的变化。RT-PCR显示TLRs在小肠和结肠不同部位的表达水平不同。TLR 4、TLR 5、TLR 7和TLR 9 mRNA在TPN给药后上调，尤其是在远端小肠系膜。TPN给药和缺乏肠内营养导致的肠道TLR上调可能与因干扰素γ介导的肠上皮细胞凋亡引起的细菌移位导致的感染性休克风险增加相关。(C)2010年爱思唯尔公司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 upregulated 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. (C) 2010 Elsevier Inc. All rights reserved.