|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0022131,
umls-concept:C0039194,
umls-concept:C0054450,
umls-concept:C0205263,
umls-concept:C0229525,
umls-concept:C0521447,
umls-concept:C1521761,
umls-concept:C1879547,
umls-concept:C2003941,
umls-concept:C2611831
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2011-1-10
|
|
pubmed:abstractText |
Cytokines contribute to pancreatic islet inflammation, leading to impaired glucose homeostasis and diabetic diseases. A plethora of data shows that proinflammatory cytokines are produced in pancreatic islets by infiltrating mononuclear immune cells. Here, we show that pancreatic islet ? cells and ? cells express tumor necrosis factor-? (TNF-?) and other cytokines capable of promoting islet inflammation when exposed to interleukin-1? (IL-1?). Cytokine expression by ? cells was dependent on calcineurin (CN)/nuclear factor of activated T cells (NFAT) and MAPK signaling. NFAT associated with the TNF-? promoter in response to stimuli and synergistically activated promoter activity with ATF2 and c-Jun. In contrast, the ?-cell-specific transcriptional activator MafA could repress NFAT-mediated TNF-? gene expression whenever C/EBP-? was bound to the promoter. NFAT differentially regulated the TNF-? gene depending upon the expression and MAPK-dependent activation of interacting basic leucine zipper partners in ? cells. Both p38 and JNK were required for induction of TNF-? mRNA and protein expression. Collectively, the data show that glucose and IL-1? can activate signaling pathways, which control induction and repression of cytokines in pancreatic endocrine cells. Thus, by these mechanisms, pancreatic ? cells themselves may contribute to islet inflammation and their own immunological destruction in the pathogenesis of diabetes.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic-Leucine Zipper Transcription...,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin,
http://linkedlifedata.com/resource/pubmed/chemical/Glucaric Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Klrg1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jan
|
|
pubmed:issn |
1083-351X
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
14
|
|
pubmed:volume |
286
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1025-36
|
|
pubmed:meshHeading |
pubmed-meshheading:21059644-Animals,
pubmed-meshheading:21059644-Basic-Leucine Zipper Transcription Factors,
pubmed-meshheading:21059644-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:21059644-Calcineurin,
pubmed-meshheading:21059644-Cells, Cultured,
pubmed-meshheading:21059644-Diabetes Mellitus, Type 1,
pubmed-meshheading:21059644-Diabetes Mellitus, Type 2,
pubmed-meshheading:21059644-Gene Expression Regulation,
pubmed-meshheading:21059644-Glucagon-Secreting Cells,
pubmed-meshheading:21059644-Glucaric Acid,
pubmed-meshheading:21059644-Insulin-Secreting Cells,
pubmed-meshheading:21059644-Interleukin-1beta,
pubmed-meshheading:21059644-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:21059644-Lectins, C-Type,
pubmed-meshheading:21059644-MAP Kinase Signaling System,
pubmed-meshheading:21059644-Membrane Glycoproteins,
pubmed-meshheading:21059644-Mice,
pubmed-meshheading:21059644-NFATC Transcription Factors,
pubmed-meshheading:21059644-Promoter Regions, Genetic,
pubmed-meshheading:21059644-Tumor Necrosis Factor-alpha,
pubmed-meshheading:21059644-p38 Mitogen-Activated Protein Kinases
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Calcineurin/nuclear factor of activated T cells and MAPK signaling induce TNF-{alpha} gene expression in pancreatic islet endocrine cells.
|
|
pubmed:affiliation |
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Michael.Lawrence@UTSouthwestern.edu
|
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|
