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TLR2、TLR4 和 MYD88 信号通路在脓毒症引起的急性肾损伤中对中性粒细胞迁移至关重要。

TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration in acute kidney injury induced by sepsis.

机构信息

Disciplina de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

出版信息

PLoS One. 2012;7(5):e37584. doi: 10.1371/journal.pone.0037584. Epub 2012 May 24.

DOI:10.1371/journal.pone.0037584
PMID:22655058
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3360043/
Abstract

The aim of this study was to investigate the role of TLR2, TLR4 and MyD88 in sepsis-induced AKI. C57BL/6 TLR2(-/-), TLR4(-/-) and MyD88(-/-) male mice were subjected to sepsis by cecal ligation and puncture (CLP). Twenty four hours later, kidney tissue and blood samples were collected for analysis. The TLR2(-/-), TLR4(-/-) and MyD88(-/-) mice that were subjected to CLP had preserved renal morphology, and fewer areas of hypoxia and apoptosis compared with the wild-type C57BL/6 mice (WT). MyD88(-/-) mice were completely protected compared with the WT mice. We also observed reduced expression of proinflammatory cytokines in the kidneys of the knockout mice compared with those of the WT mice and subsequent inhibition of increased vascular permeability in the kidneys of the knockout mice. The WT mice had increased GR1(+low) cells migration compared with the knockout mice and decreased in GR1(+high) cells migration into the peritoneal cavity. The TLR2(-/-), TLR4(-/-), and MyD88(-/-) mice had lower neutrophil infiltration in the kidneys. Depletion of neutrophils in the WT mice led to protection of renal function and less inflammation in the kidneys of these mice. Innate immunity participates in polymicrobial sepsis-induced AKI, mainly through the MyD88 pathway, by leading to an increased migration of neutrophils to the kidney, increased production of proinflammatory cytokines, vascular permeability, hypoxia and apoptosis of tubular cells.

摘要

本研究旨在探讨 TLR2、TLR4 和 MyD88 在脓毒症诱导的急性肾损伤（AKI）中的作用。C57BL/6 TLR2（-/-）、TLR4（-/-）和 MyD88（-/-）雄性小鼠通过盲肠结扎和穿刺（CLP）引发脓毒症。24 小时后，收集肾脏组织和血液样本进行分析。与野生型 C57BL/6 小鼠（WT）相比，接受 CLP 的 TLR2（-/-）、TLR4（-/-）和 MyD88（-/-）小鼠保留了肾脏形态，且缺氧和细胞凋亡区域较少。MyD88（-/-）小鼠与 WT 小鼠相比完全受到保护。与 WT 小鼠相比，我们还观察到敲除小鼠肾脏中促炎细胞因子的表达减少，随后抑制了敲除小鼠肾脏中血管通透性的增加。与敲除小鼠相比，WT 小鼠中 GR1（+低）细胞迁移增加，而 GR1（+高）细胞向腹腔的迁移减少。TLR2（-/-）、TLR4（-/-）和 MyD88（-/-）小鼠肾脏中中性粒细胞浸润减少。WT 小鼠中性粒细胞耗竭导致肾功能保护和肾脏炎症减轻。固有免疫参与多微生物脓毒症诱导的 AKI，主要通过 MyD88 途径，导致中性粒细胞向肾脏迁移增加、促炎细胞因子产生增加、血管通透性增加、肾小管细胞缺氧和细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8df3/3360043/3b3bf5bce5fb/pone.0037584.g012.jpg
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