Source:http://linkedlifedata.com/resource/pubmed/id/20412855
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
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pubmed:dateCreated |
2010-6-28
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pubmed:abstractText |
Lymphocytes participate in the early pathogenesis of ischemia-reperfusion injury (IRI) in kidney; however, their role during repair is largely unknown. Recent data have shown that Foxp3(+) regulatory T cells (Tregs) traffic into kidney during healing from IRI and directly participate in repair. Since lymphocyte-targeting therapy is currently administered to prevent rejection during recovery from IRI in renal transplants, we hypothesized that mycophenolate mofetil (MMF) would alter Treg trafficking and kidney repair. C57BL/6J and T cell deficient mice underwent unilateral clamping of renal pedicle for 45 min, followed by reperfusion, and were sacrificed at day 10. Mice were treated with saline (C) or MMF (100mg/kg) i.p. daily starting at day 2 until sacrifice (n=5-12/group). MMF worsened kidney tubular damage compared to C at 10 days (cortex and outer medulla: p<0.05) in wild-type mice; tubular apoptotic index was increased in cortex in MMF group as well (p=0.01). MMF reduced the total number of kidney-infiltrating mononuclear cells (p<0.001 versus C) and the percentages of TCRbeta(+)CD4(+) and TCRbeta(+)CD8(+) T cells (p<0.01), but not natural killer (NK), NKT or B lymphocytes. MMF specifically reduced kidney Foxp3(+) Tregs (0.82+/-0.11% versus 1.75+/-0.17%, p<0.05). Tubular proliferative index and tissue levels of basic FGF were increased in MMF group (p<0.05), IL-10 and IL-6 were decreased (p<0.05). To evaluate if MMF effect occurred through non-lymphocytic cells, T cell deficient mice were treated with MMF. Tubular injury in T cell deficient mice was not affected by MMF treatment, though MMF-treated animals had increased VEGF and decreased PDGF-BB protein tissue levels compared to controls (p<0.05). Thus, MMF modifies the structural, epithelial proliferative and inflammatory response during healing, likely through effects on T cells and possibly Tregs. Kidney repair after IRI can be altered by agents that target lymphocytes.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/FOXP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Mycophenolic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/mycophenolate mofetil
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1878-5492
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pubmed:author | |
pubmed:copyrightInfo |
Copyright (c) 2010 Elsevier B.V. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45-52
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pubmed:meshHeading |
pubmed-meshheading:20412855-Animals,
pubmed-meshheading:20412855-Disease Models, Animal,
pubmed-meshheading:20412855-Forkhead Transcription Factors,
pubmed-meshheading:20412855-Immunosuppressive Agents,
pubmed-meshheading:20412855-Kidney,
pubmed-meshheading:20412855-Kidney Tubular Necrosis, Acute,
pubmed-meshheading:20412855-Male,
pubmed-meshheading:20412855-Mice,
pubmed-meshheading:20412855-Mice, Inbred C57BL,
pubmed-meshheading:20412855-Mice, Knockout,
pubmed-meshheading:20412855-Mycophenolic Acid,
pubmed-meshheading:20412855-Reperfusion Injury,
pubmed-meshheading:20412855-T-Lymphocytes, Regulatory
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pubmed:year |
2010
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pubmed:articleTitle |
Mycophenolate mofetil modifies kidney tubular injury and Foxp3+ regulatory T cell trafficking during recovery from experimental ischemia-reperfusion.
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pubmed:affiliation |
Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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