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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0018270,
umls-concept:C0024141,
umls-concept:C0030956,
umls-concept:C0185117,
umls-concept:C0205216,
umls-concept:C0871261,
umls-concept:C1521761,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911684,
umls-concept:C2911692
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pubmed:issue |
3
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pubmed:dateCreated |
2008-1-22
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pubmed:abstractText |
Expansion of autoreactive T cells and their resistance to anergy was demonstrated in systemic lupus erythematosus (SLE). A pair of transcription factors, early growth response 2 (Egr-2) and 3 (Egr-3), are negative regulators of T cell activation that were shown to be important in anergy. A peptide (designated hCDR1 for human CDR1) based on the CDR-1 of an anti-DNA Ab ameliorated SLE in both induced and spontaneous lupus models. Our objectives were to determine the expression levels of Egr-2 and Egr-3 in autoreactive T cells following immunization with the lupus-inducing anti-DNA Ab that bears a common Id designated 16/6Id and also in a full-blown SLE and to determine the effect of hCDR1 on these transcription factors. We demonstrated diminished expression levels of Egr-2 and Egr-3 mRNA both early after immunization with the 16/6Id and in SLE-afflicted (NZB x NZW)F1 (New Zealand Black and New Zealand White) mice. Furthermore, by down-regulating Akt phosphorylation and up-regulating TGFbeta secretion, treatment with hCDR1 significantly up-regulated Egr-2 and Egr-3 expression. This was associated with an increased expression of the E3 ligase Cbl-b. Inhibition of Akt in T cells of immunized mice decreased, whereas silencing of the Egr-2 and Egr-3 in T cells of hCDR1-treated mice increased IFN-gamma secretion. Thus, hCDR1 down-regulates Akt phosphorylation, which leads to up-regulated expression of T cell Egr-2 and Egr-3, resulting in the inhibition of IFN-gamma secretion that is required for the maintenance of SLE.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 3,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/edratide
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
180
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1584-91
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18209054-Animals,
pubmed-meshheading:18209054-Antibodies, Monoclonal,
pubmed-meshheading:18209054-Clonal Anergy,
pubmed-meshheading:18209054-Early Growth Response Protein 2,
pubmed-meshheading:18209054-Early Growth Response Protein 3,
pubmed-meshheading:18209054-Humans,
pubmed-meshheading:18209054-Interferon-gamma,
pubmed-meshheading:18209054-Interleukin-2,
pubmed-meshheading:18209054-Lupus Erythematosus, Systemic,
pubmed-meshheading:18209054-Mice,
pubmed-meshheading:18209054-Mice, Inbred Strains,
pubmed-meshheading:18209054-Peptide Fragments,
pubmed-meshheading:18209054-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18209054-Phosphorylation,
pubmed-meshheading:18209054-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18209054-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:18209054-RNA, Messenger,
pubmed-meshheading:18209054-Recombinant Proteins,
pubmed-meshheading:18209054-T-Lymphocytes,
pubmed-meshheading:18209054-Transforming Growth Factor beta1,
pubmed-meshheading:18209054-Up-Regulation
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pubmed:year |
2008
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pubmed:articleTitle |
A peptide that ameliorates lupus up-regulates the diminished expression of early growth response factors 2 and 3.
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pubmed:affiliation |
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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