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Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes.
Cell Signal. 2004 Apr; 16(4):469-76.CS

Abstract

Interleukin (IL)-17 promotes cartilage breakdown by inducing matrix metalloproteinases (MMPs) and aggrecanases (a disintegrin and metalloproteinase with thrombospondin motif, ADAMTS) in arthritic joints. We investigated IL-17 signaling pathways inducing MMP-3, MMP-13 and ADAM-TS4 genes in bovine articular chondrocytes. IL-17 stimulated phosphorylation of extracellular signal-regulated kinase (ERK), protein 38 (p38) and c-Jun N-terminal kinase (JNK). ERK pathway inhibitors, PD98059 and U0126, down-regulated IL-17-induced MMP and ADAM-TS4 gene expression. Protein 38 and JNK pathway inhibitors, SB203580 and SP600125, also reduced induction of these genes. Antioxidants and activating protein-1 transcription factor inhibitors, nordihydroguaiaretic acid and N-acetyl-L-cysteine (NAC) suppressed MMP and ADAM-TS4 genes. Similarly, nuclear factor kappa B (NF-kappaB) pathways inhibitors curcumin and Bay-11-7085 also blocked their induction. Thus MMP-3, MMP-13 and ADAM-TS4 genes are coordinately up-regulated by IL-17 via MAP kinases, activating protein-1 (AP-1) and NF-kappaB mediators, which could be targeted for reducing IL-17-triggered cartilage damage.

Authors+Show Affiliations

Research Center, CHUM Hôpital Notre-Dame, K-5255 Mailloux, 1560 Sherbrooke est, Montréal, 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

14709335

Citation

Sylvester, Judith, et al. "Interleukin-17 Signal Transduction Pathways Implicated in Inducing Matrix Metalloproteinase-3, -13 and Aggrecanase-1 Genes in Articular Chondrocytes." Cellular Signalling, vol. 16, no. 4, 2004, pp. 469-76.
Sylvester J, Liacini A, Li WQ, et al. Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes. Cell Signal. 2004;16(4):469-76.
Sylvester, J., Liacini, A., Li, W. Q., & Zafarullah, M. (2004). Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes. Cellular Signalling, 16(4), 469-76.
Sylvester J, et al. Interleukin-17 Signal Transduction Pathways Implicated in Inducing Matrix Metalloproteinase-3, -13 and Aggrecanase-1 Genes in Articular Chondrocytes. Cell Signal. 2004;16(4):469-76. PubMed PMID: 14709335.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes. AU - Sylvester,Judith, AU - Liacini,Abdelhamid, AU - Li,Wen Qing, AU - Zafarullah,Muhammad, PY - 2004/1/8/pubmed PY - 2004/9/9/medline PY - 2004/1/8/entrez SP - 469 EP - 76 JF - Cellular signalling JO - Cell Signal VL - 16 IS - 4 N2 - Interleukin (IL)-17 promotes cartilage breakdown by inducing matrix metalloproteinases (MMPs) and aggrecanases (a disintegrin and metalloproteinase with thrombospondin motif, ADAMTS) in arthritic joints. We investigated IL-17 signaling pathways inducing MMP-3, MMP-13 and ADAM-TS4 genes in bovine articular chondrocytes. IL-17 stimulated phosphorylation of extracellular signal-regulated kinase (ERK), protein 38 (p38) and c-Jun N-terminal kinase (JNK). ERK pathway inhibitors, PD98059 and U0126, down-regulated IL-17-induced MMP and ADAM-TS4 gene expression. Protein 38 and JNK pathway inhibitors, SB203580 and SP600125, also reduced induction of these genes. Antioxidants and activating protein-1 transcription factor inhibitors, nordihydroguaiaretic acid and N-acetyl-L-cysteine (NAC) suppressed MMP and ADAM-TS4 genes. Similarly, nuclear factor kappa B (NF-kappaB) pathways inhibitors curcumin and Bay-11-7085 also blocked their induction. Thus MMP-3, MMP-13 and ADAM-TS4 genes are coordinately up-regulated by IL-17 via MAP kinases, activating protein-1 (AP-1) and NF-kappaB mediators, which could be targeted for reducing IL-17-triggered cartilage damage. SN - 0898-6568 UR - https://www.unboundmedicine.com/medline/citation/14709335/Interleukin_17_signal_transduction_pathways_implicated_in_inducing_matrix_metalloproteinase_3__13_and_aggrecanase_1_genes_in_articular_chondrocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898656803001888 DB - PRIME DP - Unbound Medicine ER -