TLR2, TLR4 and the MYD88 Signaling Pathway Are Crucial for Neutrophil Migration in Acute Kidney Injury Induced by Sepsis

被引:121
作者
Castoldi, Angela [1 ,2 ]
Braga, Tarcio Teodoro [2 ]
Correa-Costa, Matheus [2 ]
Aguiar, Cristhiane Favero [1 ]
Bassi, Enio Jose [2 ]
Correa-Silva, Reinaldo [1 ]
Elias, Rosa Maria [1 ]
Salvador, Fabia [1 ]
Moraes-Vieira, Pedro Manoel [2 ]
Cenedeze, Marcos Antonio [1 ]
Reis, Marlene Antonia [4 ]
Hiyane, Meire Ioshie [2 ]
Pacheco-Silva, Alvaro [1 ,3 ]
Goncalves, Giselle Martins [2 ]
Saraiva Camara, Niels Olsen [1 ,2 ]
机构
[1] Univ Fed Sao Paulo, Dept Med, Disciplina Nefrol, Sao Paulo, Brazil
[2] Univ Sao Paulo, Dept Imunol, Lab Imunobiol Transplantes, Sao Paulo, Brazil
[3] Hosp Israelita Albert Einstein, IIEP, Sao Paulo, Brazil
[4] Univ Fed Triangulo Mineiro, Uberaba, Brazil
基金
巴西圣保罗研究基金会;
关键词
ACUTE-RENAL-FAILURE; TOLL-LIKE RECEPTOR-2; NITRIC-OXIDE; ORGAN FAILURE; CELL-DEATH; LIPOPOLYSACCHARIDE; INHIBITION; EXPRESSION; APOPTOSIS; CYTOKINE;
D O I
10.1371/journal.pone.0037584
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:14
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