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


Autoria(s): Castoldi, Angela; Braga, Tarcio Teodoro; Costa, Matheus Correa; Aguiar, Cristhiane Favero de; Bassi, Ênio José; Correa-Silva, Reinaldo; Elias, Rosa Maria; Salvador, Fabia; Moraes-Vieira, Pedro Manoel; Cenedeze, Marcos Antonio; Reis, Marlene Antonia dos; Hiyane, Meire Ioshie; Filho, Álvaro Pacheco e Silva; Goncalves, Giselle Martins; Câmara, Niels Olsen Saraiva
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

06/11/2013

06/11/2013

2012

Resumo

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.

Brazilian Foundation - Fundacao de Apoio a Pesquisa do Estado de Sao Paulo (FAPESP) [07/07139-3]

Brazilian Foundation FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)

International Associated Laboratory (CNPq National Counsel of Technological and Scientific Development)

International Associated Laboratory (CNPq- National Counsel of Technological and Scientific Development)

National Institute of Science and Technology (INCT)

National Institute of Science and Technology (INCT)

Identificador

PLOS ONE, SAN FRANCISCO, v. 7, n. 5, supl. 1, Part 2, pp. 111-117, MAY 24, 2012

1932-6203

http://www.producao.usp.br/handle/BDPI/42297

10.1371/journal.pone.0037584

http://dx.doi.org/10.1371/journal.pone.0037584

Idioma(s)

eng

Publicador

PUBLIC LIBRARY SCIENCE

SAN FRANCISCO

Relação

PLOS ONE

Direitos

openAccess

Copyright PUBLIC LIBRARY SCIENCE

Palavras-Chave #ACUTE-RENAL-FAILURE #TOLL-LIKE RECEPTOR-2 #NITRIC-OXIDE #ENDOTHELIAL-CELLS #ORGAN FAILURE #RAT-KIDNEY #LIPOPOLYSACCHARIDE #APOPTOSIS #DEATH #INFLAMMATION #MULTIDISCIPLINARY SCIENCES
Tipo

article

original article

publishedVersion