Linked Life Data

17640998

Source:http://linkedlifedata.com/resource/pubmed/id/17640998

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-9-18
pubmed:abstractText
It has been suggested that Fas-mediated apoptosis plays an important role in the pathogenesis of autoimmune thyroid diseases. Our previous studies have demonstrated that normal primary thyroid epithelial cells are resistant to Fas-mediated apoptosis, but the resistance can be overcome by pretreatment with a combination of interferon-gamma (IFN-gamma) and IL-1beta. To understand the molecular mechanism responsible for the IFN-gamma/IL-1beta effects, we profiled changes in the transcription induced by these two cytokines in normal human thyroid cells, using cDNA microarrays. We found that IFN-gamma/IL-1beta showed a significant increase in apoptosis-related genes such as inducible nitric oxide synthase (iNOS), receptor-interacting protein 2 (RIP2), and caspases 10. These increases were confirmed by other methods, including real-time PCR and Western blot. Furthermore, the sensitization of primary thyroid epithelial cells to Fas-mediated apoptosis by IFN-gamma/IL-1beta was significantly blocked by a general caspase inhibitor, z-VAD, or by the combination of two specific individual caspase inhibitors. In addition, our results showed that IFN-gamma/IL-1beta enhance p38 MAPK phosphorylation and that SB 203580, a p38 MAPK inhibitor, can inhibit IFN-gamma/IL-1beta-induced p38 MAPK phosphorylation. SB 203580 also significantly prevented cytokine-induced iNOS expression and caspase activation and thus blocked Fas-mediated apoptosis of thyroid cells sensitized by IFN-gamma/IL-1beta. In conclusion, our data suggest that both p38 MAPK and iNOS are involved in IFN-gamma/IL-1beta-induced sensitization of the thyroid cells to Fas-mediated apoptosis via the activation of caspases 3, 7, and 10 and that this pathway may be further activated by BID. This hints that inflammatory cytokines regulate death-receptor-mediated apoptosis at multiple points in the process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
148
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4844-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17640998-Antigens, CD95, pubmed-meshheading:17640998-Apoptosis, pubmed-meshheading:17640998-BH3 Interacting Domain Death Agonist Protein, pubmed-meshheading:17640998-Caspases, pubmed-meshheading:17640998-Cells, Cultured, pubmed-meshheading:17640998-Enzyme Activation, pubmed-meshheading:17640998-Gene Expression Profiling, pubmed-meshheading:17640998-Gene Expression Regulation, pubmed-meshheading:17640998-Humans, pubmed-meshheading:17640998-Interferon-gamma, pubmed-meshheading:17640998-Interleukin-1beta, pubmed-meshheading:17640998-Nitric Oxide Synthase Type II, pubmed-meshheading:17640998-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17640998-Signal Transduction, pubmed-meshheading:17640998-Thyroid Gland, pubmed-meshheading:17640998-Transcription, Genetic, pubmed-meshheading:17640998-p38 Mitogen-Activated Protein Kinases
pubmed:year
2007
pubmed:articleTitle
Microarray analysis of cytokine activation of apoptosis pathways in the thyroid.
pubmed:affiliation
Department of Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0648, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural