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在小鼠内毒素血症模型中,肝脏固有免疫反应具有叶位特异性。

The hepatic innate immune response is lobe-specific in a murine model endotoxemia.

机构信息

Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, USA.

出版信息

Innate Immun. 2019 Feb;25(2):144-154. doi: 10.1177/1753425918823900.

Abstract

The liver plays a central role in the innate immune response to endotoxemia. While previous studies have demonstrated lobe-specific transcriptional responses to various insults, whether this is true in response to endotoxemia is unknown. We sought to assess whether there were significant intra- and inter-lobe differences in the murine hepatic innate immune transcriptional response to endotoxemia. Adult male ICR mice were exposed to i.p. LPS (5 mg/kg, 30 min, 60 min, 5 h) and primary ( Tnf, Cxcl1, Nfkbia, Tnfiap3) and secondary ( Il6, Nos2) innate immune response gene expression was assessed in the left medial, right medial, left lateral, and right lateral lobes, and the papillary and caudate processes. The expression of all innate immune response genes increased following i.p. LPS challenge. When tested at the early time points (30 and 60 min), the left medial lobe and caudate process consistently demonstrated the highest induction of gene expression. Most inter-lobe differences were attenuated at later time points (5 h). To improve reproducibility of the study of endotoxemia induced by i.p. LPS challenge, inclusion of appropriate methodological details regarding collection of hepatic tissue should be included when reporting scientific results in published manuscripts.

摘要

肝脏在对内毒素血症的固有免疫反应中起着核心作用。虽然先前的研究已经证明了不同叶位对各种损伤的特定转录反应,但这种情况是否适用于对内毒素血症尚不清楚。我们试图评估内毒素血症是否会导致小鼠肝脏固有免疫转录反应在叶内和叶间存在显著差异。成年雄性 ICR 小鼠接受腹腔内 LPS(5mg/kg,30 分钟,60 分钟,5 小时)处理,并评估左中、右中、左外和右外侧叶以及乳头和尾状突中初级(TNF、CXCL1、NFKBIA、TNFAIP3)和次级(IL6、NOS2)固有免疫反应基因的表达。在腹腔内 LPS 挑战后,所有固有免疫反应基因的表达均增加。在早期时间点(30 分钟和 60 分钟)检测时,左中叶和尾状突始终表现出最高的基因表达诱导。大多数叶间差异在后期(5 小时)减弱。为了提高腹腔内 LPS 挑战引起的内毒素血症研究的可重复性,在发表的科学论文中报告科学结果时,应包括有关肝脏组织采集的适当方法细节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbe6/6830862/1c2b75bcf6d5/10.1177_1753425918823900-fig1.jpg

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