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Date: December 2010

Journal: Kidney International Volume 78, Issue 11, December 2010, Pages 1100-1109 , Doi: 10.1038/ki.2010.139

2010 | CD4+ CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice…

Lee, H.a, Nho, D.a, Chung, H.-S.a, Lee, H.a, Shin, M.-K.a, Kim, S.-H.b, Bae, H.a

Abstract

Nephrotoxicity limits the use of cisplatin, a widely used chemotherapeutic agent for treatment of various malignancies. Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+ CD25 + regulatory T-cell subset (CD4+ CD25+ Treg) has broad suppressive effects on many different cell types. In this study, we determined whether CD4+ CD25+ Treg cells had protective effects against cisplatin-induced acute renal injury in nu/nu mice that lack mature T cells. In these mice, there was marked attenuation of the decreased survival, renal dysfunction and tubular injury, renal tumor necrosis factor-α, and interleukin-1Β cytokine levels. Furthermore, renal macrophage accumulation was reduced in CD4+ CD25+ Treg cell-adoptive transferred nu/nu mice compared with control mice. Infusion of CD4+ CD25+ Treg cells into wild-type Balb/c mice reduced serum blood urea nitrogen and creatinine levels equivalent to those in nu/nu mice and extended their survival time after cisplatin injection. In contrast, depletion of CD4+ CD25+ Treg cells in wild-type mice exacerbated kidney injury after cisplatin administration. Transcription factor Foxp3-positive cells (Treg cells) were detected in the kidneys of nu/nu mice after cisplatin injection. Our results suggest that CD4+ CD25 + Treg cells directly affect cisplatin nephrotoxicity and their modulation represents an additional treatment strategy. © 2010 International Society of Nephrology.


Author keywords

cisplatin; nephrotoxicity; regulatory T cell


Indexed keywords

EMTREE drug terms: cisplatin; creatinine; interleukin 1beta; transcription factor FOXP3; tumor necrosis factor alpha

EMTREE medical terms: animal experiment; animal model; article; CD4+ CD25+ T lymphocyte; controlled study; creatinine blood level; kidney dysfunction; kidney injury; kidney tubule damage; macrophage; male; mouse; nephrotoxicity; nonhuman; nude mouse; priority journal; regulatory T lymphocyte; single drug dose; urea nitrogen blood level

MeSH: Adoptive Transfer; Animals; Biological Markers; Blood Urea Nitrogen; Chemotaxis, Leukocyte; Cisplatin; Creatinine; Disease Models, Animal; Forkhead Transcription Factors; Immunity, Innate; Inflammation Mediators; Interleukin-1beta; Interleukin-2 Receptor alpha Subunit; Kidney; Kidney Diseases; Macrophages; Male; Mice; Mice, Inbred BALB C; Mice, Nude; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Time Factors; Tumor Necrosis Factor-alpha
Medline is the source for the MeSH terms of this document.


Chemicals and CAS Registry Numbers: cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; creatinine, 19230-81-0, 60-27-5;Biological Markers; Cisplatin, 15663-27-1; Creatinine, 60-27-5; Forkhead Transcription Factors; Foxp3 protein, mouse; IL2RA protein, human; Inflammation Mediators; Interleukin-1beta; Interleukin-2 Receptor alpha Subunit; Tumor Necrosis Factor-alpha

Manufacturers:Drug manufacturer: Sigma Aldrich, United States.


ISSN: 00852538 CODEN: KDYIASource Type: Journal Original language: English
DOI: 10.1038/ki.2010.139 PubMed ID: 20463654 Document Type: Article
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