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Infusion of IL-10-expressing cells protects against renal ischemia through induction of lipocalin-2.
MedLine Citation:
PMID:  22278021     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.Kidney International advance online publication, 25 January 2012; doi:10.1038/ki.2011.446.
Authors:
Michaela Jung; Anna Sola; Jeremy Hughes; David C Kluth; Eugenia Vinuesa; Jose Luis Viñas; Albert Pérez-Ladaga; Georgina Hotter
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-25
Journal Detail:
Title:  Kidney international     Volume:  -     ISSN:  1523-1755     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Department of Ischemia and Inflammation, IIBB-CSIC-IDIBAPS, Experimental Pathology, Barcelona, Spain [2] Institute of Biochemistry I/ZAFES, Goethe-University Frankfurt, Frankfurt, Germany.
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