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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2008-8-21
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pubmed:abstractText |
Cytokines contribute to pancreatic beta-cell apoptosis in type 1 diabetes (T1D) by modulation of beta-cell gene expression networks. The transcription factor Activator Protein-1 (AP-1) is a key regulator of inflammation and apoptosis. We presently evaluated the function of the AP-1 subunit JunB in cytokine-mediated beta-cell dysfunction and death. The cytokines IL-1beta+IFN-gamma induced an early and transitory upregulation of JunB by NF-kappaB activation. Knockdown of JunB by RNA interference increased cytokine-mediated expression of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum (ER) stress markers, leading to increased apoptosis in an insulin-producing cell line (INS-1E) and in purified rat primary beta-cells. JunB knockdown beta-cells and junB(-/-) fibroblasts were also more sensitive to the chemical ER stressor cyclopiazonic acid (CPA). Conversely, adenoviral-mediated overexpression of JunB diminished iNOS and ER markers expression and protected beta-cells from cytokine-induced cell death. These findings demonstrate a novel and unexpected role for JunB as a regulator of defense mechanisms against cytokine- and ER stress-mediated apoptosis.
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pubmed:commentsCorrections |
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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 |
1932-6203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e3030
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18716665-3T3 Cells,
pubmed-meshheading:18716665-Adenoviridae,
pubmed-meshheading:18716665-Animals,
pubmed-meshheading:18716665-Apoptosis,
pubmed-meshheading:18716665-Cell Death,
pubmed-meshheading:18716665-Cells, Cultured,
pubmed-meshheading:18716665-Endoplasmic Reticulum,
pubmed-meshheading:18716665-Fibroblasts,
pubmed-meshheading:18716665-Gene Deletion,
pubmed-meshheading:18716665-Genetic Vectors,
pubmed-meshheading:18716665-Insulin-Secreting Cells,
pubmed-meshheading:18716665-Mice,
pubmed-meshheading:18716665-Nitric Oxide,
pubmed-meshheading:18716665-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:18716665-Rats,
pubmed-meshheading:18716665-Rats, Wistar
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pubmed:year |
2008
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pubmed:articleTitle |
JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells.
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pubmed:affiliation |
Laboratory of Experimental Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
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pubmed:publicationType |
Journal Article
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