Infusion of IL-10-expressing cells protects against renal ischemia through induction of lipocalin-2.
Kidney Int
; 81(10): 969-982, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22278021
ABSTRACT
Ischemia/reperfusion injury is a leading cause of acute renal failure triggering an inflammatory response associated with infiltrating macrophages, which determine disease outcome. To repair the inflammation we designed a procedure whereby macrophages that overexpress the anti-inflammatory agent interleukin (IL)-10 were adoptively transferred. These bone marrow-derived macrophages were able to increase their intracellular iron pool that, in turn, augmented the expression of lipocalin-2 and its receptors. Infusion of these macrophages into rats after 1 h of reperfusion resulted in localization of the cells to injured kidney tissue, caused increases in regenerative markers, and a notable reduction in both blood urea nitrogen and creatinine. Furthermore, IL-10 therapy decreased the local inflammatory profile and upregulated the expression of pro-regenerative lipocalin-2 and its receptors. IL-10-mediated protection and subsequent renal repair were dependent on the presence of iron and lipocalin-2, since the administration of a neutralizing antibody for lipocalin-2 or administration of IL-10 macrophages pretreated with the iron chelating agent deferoxamine abrogated IL-10-mediated protective effects. Thus, adoptive transfer of IL-10 macrophages to ischemic kidneys blunts acute kidney injury. These effects are mediated through the action of intracellular iron to induce lipocalin-2.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Interleucina-10
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Transferência Adotiva
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Lipocalinas
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Injúria Renal Aguda
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Isquemia
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Rim
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Macrófagos
Idioma:
En
Revista:
Kidney Int
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha