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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.
Exp Cell Res. 2003 Aug 01; 288(1):208-17.EC

Abstract

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.

Authors+Show Affiliations

Department of Medicine and Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

12878172

Citation

Liacini, Abdelhamid, et al. "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." Experimental Cell Research, vol. 288, no. 1, 2003, pp. 208-17.
Liacini A, Sylvester J, Li WQ, et al. 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. Exp Cell Res. 2003;288(1):208-17.
Liacini, A., Sylvester, J., Li, W. Q., Huang, W., Dehnade, F., Ahmad, M., & Zafarullah, M. (2003). 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. Experimental Cell Research, 288(1), 208-17.
Liacini A, et al. 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. Exp Cell Res. 2003 Aug 1;288(1):208-17. PubMed PMID: 12878172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Liacini,Abdelhamid, AU - Sylvester,Judith, AU - Li,Wen Qing, AU - Huang,Wensheng, AU - Dehnade,Faramaze, AU - Ahmad,Mushtaq, AU - Zafarullah,Muhammad, PY - 2003/7/25/pubmed PY - 2003/9/25/medline PY - 2003/7/25/entrez SP - 208 EP - 17 JF - Experimental cell research JO - Exp Cell Res VL - 288 IS - 1 N2 - 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. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/12878172/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014482703001800 DB - PRIME DP - Unbound Medicine ER -