Exp Cell Res 2003,
PMID: 12878172
Liacini, Abdelhamid; Sylvester, Judith; Li, Wen Qing; Huang, Wensheng; Dehnade, Faramaze; Ahmad, Mushtaq; Zafarullah, Muhammad
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.
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Text Mining Data
matrix metalloproteinase-13 → TNF-alpha: "
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
"
matrix metalloproteinase-13 → AP-1: "
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
"
mitogen activated protein ( MAP ) kinases → TNF-alpha: "
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
"
p38 → TNF-alpha: "
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
"
MMP-13 → TNF: "
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
"
MMP-13 → TNF-alpha: "
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
"
MMP-13 → TNF-alpha: "
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
"
MMP-13 → ERK: "
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
"
MMP-13 → p38: "
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
"
Manually curated Databases
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OpenBEL Selventa BEL large corpus:
MAPK9
→
TNF
(increases, TNF Activity)
Evidence: JNK2 gets activated in primary human femoral head chondrocytes exposed to TNF-alpha for 20 min.
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OpenBEL Selventa BEL large corpus:
MAPK9
→
TNF
(increases, TNF Activity)
Evidence: Treatment of cells with a combination of TNF alpha and IL1 beta activated the p46JNK (JNK1) and p55JNK(JNK2). JNKs activation was apparent after 5 min and peaked at 20 min.
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OpenBEL Selventa BEL large corpus:
MAPK8
→
IL1B
(increases, IL1B Activity)
Evidence: Treatment of cells with a combination of TNF alpha and IL1 beta activated the p46JNK (JNK1) and p55JNK(JNK2). JNKs activation was apparent after 5 min and peaked at 20 min.