Linked Life Data

12878172

Source:http://linkedlifedata.com/resource/pubmed/id/12878172

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-7-24
pubmed:abstractText
Tumor necrosis factor alpha (TNF-alpha), a major proinflammatory cytokine, induces arthritic joint inflammation and resorption of cartilage by matrix metalloproteinase-13 (MMP-13). RNA for MMP-13 is increased in human arthritic femoral cartilage. Mechanisms of this induction were investigated by pretreating primary human osteoarthritic (OA) femoral head chondrocytes or chondrosarcoma cells with the potential inhibitors of TNF-alpha signal transduction and downstream target transcription factors followed by stimulation with TNF-alpha and analysis of MMP-13 RNA/protein. TNF-alpha rapidly activated phosphorylation of extracellular signal-regulated kinases (ERKs), p38, and c-jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinases in human chondrocytes. Inhibitors of ERK (U0126, PD98059, and ERK1/2 antisense phosphorothioate oligonucleotide), JNK (SB203580, SP600125, and curcumin), and p38 (SB203580 and SB202190) pathways down-regulated the TNF-stimulated expression of MMP-13. Inhibitors of the transcription factors AP-1 (nordihydroguaiaretic acid, NDGA) and NF-kappaB (curcumin, proteasome inhibitors, and Bay-11-7085) suppressed TNF-alpha-induced MMP-13 expression in primary chondrocytes and SW1353 cells. These results suggest that induction of the MMP-13 gene by TNF-alpha is mediated by ERK, p38, and JNK MAP kinases as well as AP-1 and NF-kappaB transcription factors. Blockade of TNF-alpha signaling and its target transcription factors by the approaches tested here may be beneficial for reducing cartilage breakdown by MMP-13 in arthritis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Collagenases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein..., http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4, http://linkedlifedata.com/resource/pubmed/chemical/MMP13 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 13, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase..., http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1, http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
208-17
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Induction of matrix metalloproteinase-13 gene expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes.
pubmed:affiliation
Department of Medicine and Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't