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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2001-10-19
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pubmed:abstractText |
The antithyroid drug, methimazole (MMI) is used to treat patients with Graves' hyperthyroidism. The major action of MMI is to inhibit synthesis of thyroid hormone in the thyroid gland. However, MMI also has antioxidant and immunomodulatory effects on thyrocytes and/or immune cells. This study identifies novel antioxidant and immunomodulatory effects of MMI involving the interferon-gamma (IFN-gamma) signaling pathway in thyroid cells. MMI inhibits transcription of the intercellular adhesion molecule-1 (ICAM-1) gene by modulating the function of transcription factor STAT1 (signal transducer and activator of transcription 1), which binds to the IFN-gamma activated site of the ICAM-1 promoter. Furthermore, MMI rapidly eliminates H(2)O(2) produced by IFN-gamma treatment in thyroid cells and thus inhibits the H(2)O(2)-mediated phosphorylation of tyrosine 701 in STAT1. MMI also eliminates H(2)O(2) in vitro. MMI facilitates electron transfer from NADPH to H(2)O(2) using thioredoxin or glutathione, fulfilling a role similar to peroxiredoxin or glutathione peroxidase, respectively. MMI prevents the IFN-gamma and H(2)O(2)-mediated reversible inactivation of phosphatases. These effects inhibit full activation of the IFN-gamma-induced Janus kinase(JAK)/STAT signaling pathway in FRTL-5 thyroid cells. These results may in part explain the antioxidant and immunomodulatory effects of MMI in thyroid cells of Graves' disease patients.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Jak1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Methimazole,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidases,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxiredoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Inhibitors of Activated STAT,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Socs1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0026-895X
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pubmed:author |
pubmed-author:AGREC LCL,
pubmed-author:ChungH KHK,
pubmed-author:EsuM PMP,
pubmed-author:GowAA,
pubmed-author:GutV AVA,
pubmed-author:HwangY SYS,
pubmed-author:KimHH,
pubmed-author:KimK HKH,
pubmed-author:KwonO YOY,
pubmed-author:LeeT HTH,
pubmed-author:ShonsAA,
pubmed-author:YuD YDY
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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 |
972-80
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11641425-Animals,
pubmed-meshheading:11641425-Thyroid Gland,
pubmed-meshheading:11641425-Proteins,
pubmed-meshheading:11641425-Rats,
pubmed-meshheading:11641425-Tyrosine,
pubmed-meshheading:11641425-Hydrogen Peroxide,
pubmed-meshheading:11641425-Phosphorylation,
pubmed-meshheading:11641425-Kinetics,
pubmed-meshheading:11641425-Peroxidases,
pubmed-meshheading:11641425-Antioxidants,
pubmed-meshheading:11641425-Cells, Cultured,
pubmed-meshheading:11641425-Protein Biosynthesis,
pubmed-meshheading:11641425-Electron Transport,
pubmed-meshheading:11641425-Adjuvants, Immunologic,
pubmed-meshheading:11641425-Methimazole,
pubmed-meshheading:11641425-Drug Interactions,
pubmed-meshheading:11641425-Carrier Proteins,
pubmed-meshheading:11641425-Repressor Proteins,
pubmed-meshheading:11641425-Signal Transduction,
pubmed-meshheading:11641425-DNA-Binding Proteins,
pubmed-meshheading:11641425-Transcription Factors,
pubmed-meshheading:11641425-Interferon-gamma,
pubmed-meshheading:11641425-Gene Expression,
pubmed-meshheading:11641425-Protein-Tyrosine Kinases,
pubmed-meshheading:11641425-Trans-Activators,
pubmed-meshheading:11641425-Proto-Oncogene Proteins,
pubmed-meshheading:11641425-Peroxiredoxins,
pubmed-meshheading:11641425-Intercellular Adhesion Molecule-1,
pubmed-meshheading:11641425-Janus Kinase 1,
pubmed-meshheading:11641425-Janus Kinase 2,
pubmed-meshheading:11641425-STAT1 Transcription Factor,
pubmed-meshheading:11641425-STAT3 Transcription Factor,
pubmed-meshheading:11641425-Suppressor of Cytokine Signaling Proteins
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