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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-2
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pubmed:dateCreated |
2004-7-7
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pubmed:abstractText |
Inhibition of the 26S proteasome reduces the severity of several immune-mediated diseases. Here, we report that the proteasome also regulates transfer-induced diabetes in nonobese mice. Treatment of recipient mice with the proteasome inhibitor N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal (MG132) resulted in a 76% reduction in transfer-induced diabetes. The closely related inhibitor carbobenzoxy-l-leucyl-l-leucinal that inhibits calpains but not the proteasome had no protective effect, suggesting that MG132 acted via inhibition of the proteasome. MG132 decreased proliferation of transferred T cells in the pancreatic lymph nodes in vivo and prevented their expansion in a dose-dependent manner in vitro, consistent with a direct effect by MG132 on the T cells. MG132 did not prevent migration of transferred T cells into the islets but reduced the number of mice with severe infiltration. We suggest that MG132 prevents transfer-induced diabetes by directly targeting the autoreactive T cells and lowering their diabetogenic potential.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
0300-9475
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
134-42
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15238082-Adoptive Transfer,
pubmed-meshheading:15238082-Animals,
pubmed-meshheading:15238082-Cell Division,
pubmed-meshheading:15238082-Cysteine Endopeptidases,
pubmed-meshheading:15238082-Cysteine Proteinase Inhibitors,
pubmed-meshheading:15238082-Diabetes Mellitus, Experimental,
pubmed-meshheading:15238082-Diabetes Mellitus, Type 1,
pubmed-meshheading:15238082-Flow Cytometry,
pubmed-meshheading:15238082-Glycosuria,
pubmed-meshheading:15238082-Islets of Langerhans,
pubmed-meshheading:15238082-Leupeptins,
pubmed-meshheading:15238082-Lymph Nodes,
pubmed-meshheading:15238082-Lymphocyte Activation,
pubmed-meshheading:15238082-Mice,
pubmed-meshheading:15238082-Mice, Inbred NOD,
pubmed-meshheading:15238082-Mice, Transgenic,
pubmed-meshheading:15238082-Multienzyme Complexes,
pubmed-meshheading:15238082-Proteasome Endopeptidase Complex,
pubmed-meshheading:15238082-T-Lymphocytes
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pubmed:articleTitle |
Inhibition of the proteasome reduces transfer-induced diabetes in nonobese diabetic mice.
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pubmed:affiliation |
Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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