Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4.

Détails

ID Serval
serval:BIB_D1CAA0DE9013
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4.
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Allam R., Scherbaum C.R., Darisipudi M.N., Mulay S.R., Hägele H., Lichtnekert J., Hagemann J.H., Rupanagudi K.V., Ryu M., Schwarzenberger C., Hohenstein B., Hugo C., Uhl B., Reichel C.A., Krombach F., Monestier M., Liapis H., Moreth K., Schaefer L., Anders H.J.
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Statut éditorial
Publié
Date de publication
2012
Volume
23
Numéro
8
Pages
1375-1388
Langue
anglais
Résumé
In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-κB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI.
Mots-clé
Acute Kidney Injury/immunology, Acute Kidney Injury/metabolism, Animals, Capillary Permeability, Cytokines/metabolism, Endothelial Cells/physiology, Epithelial Cells/metabolism, Histones/metabolism, Injections, Intra-Arterial, Kidney/pathology, Kidney Tubules/metabolism, Leukocytes/physiology, Lipopolysaccharides, Mice, Mice, Inbred C57BL, Myeloid Differentiation Factor 88/metabolism, Necrosis, Renal Artery, Reperfusion Injury/prevention & control, Toll-Like Receptor 2/metabolism, Toll-Like Receptor 4/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/11/2012 19:43
Dernière modification de la notice
09/05/2019 1:37
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