TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration in acute kidney injury induced by sepsis.
TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration in acute kidney injury induced by sepsis.
复制标题
DOI：
10.1371/journal.pone.0037584
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Saraiva Câmara NO
中科院分区：
文献类型：
--
作者：
Castoldi A;Braga TT;Correa-Costa M;Aguiar CF;Bassi ÊJ;Correa-Silva R;Elias RM;Salvador F;Moraes-Vieira PM;Cenedeze MA;Reis MA;Hiyane MI;Pacheco-Silva Á;Gonçalves GM;Saraiva Câmara NO
本研究的目的是探讨 TLR2、TLR4 和 MyD88 在脓毒症诱发的 AKI 中的作用。通过盲肠结扎和穿刺（CLP）使 C57BL/6 TLR2−/−、TLR4−/− 和 MyD88−/− 雄性小鼠患败血症。二十四小时后，收集肾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，缺氧和凋亡区域更少。与 WT 小鼠相比，MyD88−/− 小鼠受到完全保护。我们还观察到与 WT 小鼠相比，敲除小鼠肾脏中促炎细胞因子的表达减少，并且随后抑制了敲除小鼠肾脏中血管通透性增加。与敲除小鼠相比，WT小鼠的GR1+低细胞迁移增加，而GR1+高细胞向腹膜腔的迁移减少。 TLR2−/−、TLR4−/− 和 MyD88−/− 小鼠的肾脏中性粒细胞浸润较低。 WT 小鼠中中性粒细胞的消耗可以保护肾功能并减少这些小鼠肾脏的炎症。先天免疫主要通过 MyD88 途径参与多种微生物脓毒症诱发的 AKI，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、缺氧和肾小管细胞凋亡。
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.
登录
查看更多内容
DOI：
10.4049/jimmunol.182.1.581
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Komura H;Miksa M;Wu R;Goyert SM;Wang P
通讯作者：
Wang P
影响因子：
2
作者：
Messaris, Evangelos;Memos, Nikolaos;Bramis, John
通讯作者：
Bramis, John
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
DOI：
10.1073/pnas.96.25.14541
发表时间：
1999-12-07
影响因子：
11.1
作者：
Hotchkiss, RS;Tinsley, KW;Karl, IE
通讯作者：
Karl, IE
DOI：
10.1016/s0162-3109(99)00095-8
发表时间：
1999-09-01
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Carattino, MD;Cueva, F;Catanzaro, OL
通讯作者：
Catanzaro, OL