Toll-like receptor 4 is protective against neonatal murine ischemia-reperfusion intestinal injury.
Toll-like receptor 4 is protective against neonatal murine ischemia-reperfusion intestinal injury.
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DOI：
10.1016/j.jpedsurg.2010.02.093
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发表时间：
2010-06
影响因子：
2.4
通讯作者：
Dimmitt RA
中科院分区：
文献类型：
--
作者：
Tatum PM Jr;Harmon CM;Lorenz RG;Dimmitt RA
接受益生菌治疗的早产儿坏死性小肠结肠炎的发病率降低。这可能是由肠道细菌信号通过Toll样受体（TLR）2和4维持肠道稳态介导的。我们假设TLR 2和TLR 4对缺血再灌注（I/R）肠损伤具有保护作用。两周龄的C57 BL/6野生型（WT）、B6.TLR2-/-、B6.TLR4-/-、B6.TLR2-/-4-/-和微生物减少（抗生素处理）小鼠（MR）进行60分钟的上级肠系膜动脉闭塞（I），随后进行90分钟的再灌注（R）。收集小肠，采用定量PCR分析显微镜下损伤、细胞凋亡和炎症基因表达。I/R后，B6.TLR4−/−、B6.TLR2−/−4−/−和MR幼仔的中位组织学损伤评分高于WT或B6.TLR2−/−幼仔，这与基于TUNEL和活化caspase-3免疫染色的更大细胞凋亡相对应。B6.TLR4−/−、B6.TLR2−/−4−/−和MR也具有升高的组织先天免疫相关趋化因子和细胞因子表达缺乏TLR 4的新生小鼠，无论是单独还是也缺乏TLR 2，以及缺乏正常肠道微生物组的那些小鼠对肠损伤的I/R模型更敏感。这些结果可能为益生菌介导的保护作用提供了一种机制，这可能有助于指导进一步研究益生菌的保护机制。
Premature infants receiving probiotics have a decreased incidence of necrotizing enterocolitis. This may be mediated by intestinal bacterial signaling via toll-like receptors (TLRs) 2 and 4 maintaining intestinal homeostasis. We hypothesized that TLRs 2 and 4 are protective against ischemia-reperfusion (I/R) intestinal injury. Two-week-old C57BL/6 wild-type (WT), B6.TLR2−/−, B6.TLR4−/−, B6.TLR2−/− 4−/−, and microbially reduced (antibiotic treated) mice (MR) underwent 60 minutes of superior mesenteric artery occlusion (I) followed by 90 minutes of reperfusion (R). Small intestine was harvested for analysis of microscopic injury, apoptosis, and inflammatory gene expression using quantitative PCR. Following I/R, the median histological injury scores of the B6.TLR4−/−, B6.TLR2−/−4−/−, and MR pups were higher than the WT or B6.TLR2−/− pups which corresponded with greater apoptosis based on TUNEL and activated caspase-3 immunostaining. B6.TLR4−/−, B6.TLR2−/−4−/−, and MR also had elevated tissue innate immunity associated chemokine and cytokine expression Neonatal mice deficient in TLR4, either alone or also deficient in TLR2, as well as those lacking a normal commensal intestinal microbiome are more susceptible to an I/R model of intestinal injury. These results may provide a mechanism for commensal bacterial-mediated protection, which may help to direct further studies to elucidate the mechanism of probiotic protection.
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影响因子：
3.6
作者：
Jilling, T;Lu, J;Caplan, MS
通讯作者：
Caplan, MS
影响因子：
4.1
作者：
Aprahamian, Charles J.;Lorenz, Robin G.;Dimmit, Reed A.
通讯作者：
Dimmit, Reed A.
影响因子：
2.5
作者：
Abreu, MT
通讯作者：
Abreu, MT
DOI：
10.1038/nri2587
发表时间：
2009-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Claud, EC;Walker, WA
通讯作者：
Walker, WA