PMID- 12009331
OWN - NLM
STAT- MEDLINE
DCOM- 20021203
LR  - 20220317
IS  - 0945-053X (Print)
IS  - 0945-053X (Linking)
VI  - 21
IP  - 3
DP  - 2002 Apr
TI  - Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) 
      and nuclear factor kappa B (NF-kappa B) transcription factors down-regulates 
      matrix metalloproteinase gene expression in articular chondrocytes.
PG  - 251-62
AB  - Interleukin-1 (IL-1), the main cytokine instigator of cartilage degeneration in 
      arthritis, induces matrix metalloproteinase-3 (MMP-3) and MMP-13 RNA and protein 
      in chondrocytes. The molecular mechanisms of this induction were investigated 
      with specific inhibitors of mitogen-activated protein kinase (MAPK) signaling 
      pathways and activating protein (AP-1) and nuclear factor kappa B (NF-kappa B) 
      transcription factors. IL-1 rapidly induced the activation of 
      extracellular-signal regulated kinase (ERK), protein 38 (p38) and c-Jun 
      N-terminal kinase (JNK) MAPKs in the first-passage human femoral head OA 
      chondrocytes. The ERK-MAPK pathway inhibitor, PD98059, attained 46-53% (MMP-3) 
      and 59-66% (MMP-13) inhibition of RNA induction in human OA and 47-52% (MMP-3) 
      and 69-73% (MMP-13) inhibition in bovine chondrocytes. U0126 conferred 37-77% 
      (MMP-3) and 43-73% (MMP-13) suppression in human and 77-100% (MMP-3) and 96-100% 
      (MMP-13) in bovine chondrocytes. P38 and JNK inhibitor, SB203580 caused 35-37% 
      reduction of MMP-3 and MMP-13 RNA in human and 36-46% (MMP-3) and 60-88% (MMP-13) 
      in bovine chondrocytes. Inhibitor of JNK, AP-1 and NF-kappa B, curcumin, achieved 
      48-99% suppression of MMP-3 and 45-97% of MMP-13 in human and 8-100% (MMP-3) and 
      32-100% (MMP-13) in bovine chondrocytes. NF-kappaB inhibitor, pyrrolidine 
      dithiocarbamate yielded 83-84% reduction of MMP-3 and 38-55% for MMP-13 in human 
      chondrocytes. In bovine chondrocytes, the induction decreased by 54-64% for MMP-3 
      and 74-93% for MMP-13 RNA. These results suggest the involvement of MAPKs, AP-1 
      and NF-kappa B transcription factors in the IL-1 induction of MMPs in 
      chondrocytes. Inhibition of IL-1 signal transduction by these agents could be 
      useful for reducing cartilage resorption by MMPs in arthritis.
FAU - Liacini, Abdelhamid
AU  - Liacini A
AD  - Departement de Medecine and Centre de Recherche du Centre Hospitalier de 
      l'Universite de Montreal, Hopital Notre-Dame du CHUM, 1560 Sherbrooke est, 
      Montreal, Quebec, Canada H2L 4M1.
FAU - Sylvester, Judith
AU  - Sylvester J
FAU - Li, Wen Qing
AU  - Li WQ
FAU - Zafarullah, Muhammad
AU  - Zafarullah M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Matrix Biol
JT  - Matrix biology : journal of the International Society for Matrix Biology
JID - 9432592
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyridines)
RN  - 0 (Pyrrolidines)
RN  - 0 (Thiocarbamates)
RN  - 0 (Transcription Factor AP-1)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - IT942ZTH98 (Curcumin)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Animals
MH  - Cartilage, Articular/cytology
MH  - Cattle
MH  - Cells, Cultured
MH  - Chondrocytes/cytology/drug effects/immunology
MH  - Collagenases/*genetics
MH  - Curcumin/pharmacology
MH  - *Down-Regulation
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Femur Head/cytology/immunology
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Interleukin-1/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Matrix Metalloproteinase 13
MH  - Matrix Metalloproteinase 3/*genetics
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Osteoarthritis, Hip/*enzymology/immunology/pathology
MH  - Pyridines/pharmacology
MH  - Pyrrolidines/pharmacology
MH  - Thiocarbamates/pharmacology
MH  - Time Factors
MH  - Transcription Factor AP-1/*antagonists & inhibitors
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2002/05/16 10:00
MHDA- 2002/12/04 04:00
CRDT- 2002/05/16 10:00
PHST- 2002/05/16 10:00 [pubmed]
PHST- 2002/12/04 04:00 [medline]
PHST- 2002/05/16 10:00 [entrez]
AID - S0945053X02000070 [pii]
AID - 10.1016/s0945-053x(02)00007-0 [doi]
PST - ppublish
SO  - Matrix Biol. 2002 Apr;21(3):251-62. doi: 10.1016/s0945-053x(02)00007-0.