A synthetic triterpenoid selectively inhibits the induction of matrix metalloproteinases 1 and 13 by inflammatory cytokines
| Autor: | K S, Mix, J A, Mengshol, U, Benbow, M P, Vincenti, M B, Sporn, C E, Brinckerhoff |
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| Rok vydání: | 2001 |
| Předmět: |
Chondrosarcoma
Bone Neoplasms Gene Expression Regulation Enzymologic Extracellular Matrix Substrate Specificity Cell Movement Matrix Metalloproteinase 13 Osteoarthritis Tumor Cells Cultured Humans Collagen Collagenases RNA Messenger Matrix Metalloproteinase 1 Oleanolic Acid Cell Division Interleukin-1 RNA Nuclear |
| Zdroj: | Arthritis and rheumatism. 44(5) |
| ISSN: | 0004-3591 |
| Popis: | To address the effects of a novel synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), on the induction of matrix metalloproteinases 1 and 13 (MMP-1, MMP-13) by inflammatory cytokines.Human chondrosarcoma cells stimulated with inflammatory cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor alpha) were used to study the effects of CDDO on the induction of MMPs and the invasion of cells through a collagen matrix.CDDO selectively reduced the induction of MMP-1 and MMP-13 at the levels of messenger RNA and protein. Treatment with CDDO prior to cytokine stimulation enhanced this inhibition, and we demonstrated that CDDO functions at the level of transcription. Additionally, CDDO reduced IL-1beta-mediated invasion of cells through a collagen matrix.This study demonstrates that CDDO is a novel inhibitor of MMP-1 and MMP-13 gene expression mediated by inflammatory cytokines. Thus, CDDO may have therapeutic potential for the inhibition of joint degradation in osteoarthritis. |
| Databáze: | OpenAIRE |
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