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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.
Matrix Biol. 2002 Apr; 21(3):251-62.MB

Abstract

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.

Authors+Show Affiliations

Département de Médecine and Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame du CHUM, 1560 Sherbrooke est, Montreal, Québec, Canada H2L 4M1.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12009331

Citation

Liacini, Abdelhamid, et al. "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." Matrix Biology : Journal of the International Society for Matrix Biology, vol. 21, no. 3, 2002, pp. 251-62.
Liacini A, Sylvester J, Li WQ, et al. 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. Matrix Biol. 2002;21(3):251-62.
Liacini, A., Sylvester, J., Li, W. Q., & Zafarullah, M. (2002). 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. Matrix Biology : Journal of the International Society for Matrix Biology, 21(3), 251-62.
Liacini A, et al. 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. Matrix Biol. 2002;21(3):251-62. PubMed PMID: 12009331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Liacini,Abdelhamid, AU - Sylvester,Judith, AU - Li,Wen Qing, AU - Zafarullah,Muhammad, PY - 2002/5/16/pubmed PY - 2002/12/4/medline PY - 2002/5/16/entrez SP - 251 EP - 62 JF - Matrix biology : journal of the International Society for Matrix Biology JO - Matrix Biol VL - 21 IS - 3 N2 - 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. SN - 0945-053X UR - https://www.unboundmedicine.com/medline/citation/12009331/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0945053X02000070 DB - PRIME DP - Unbound Medicine ER -