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Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis.

Shakibaei, M, John, T, Schulze-Tanzil, G, Lehmann, I and Mobasheri, A (2007) Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis. Biochem Pharmacol, 73 (9). pp. 1434-1445.

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Abstract

Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) play a key role in the pathogenesis of osteoarthritis (OA). Anti-inflammatory agents capable of suppressing the production and catabolic actions of these cytokines may have therapeutic potential in the treatment of OA and a range of other osteoarticular disorders. The purpose of this study was to examine the effects of curcumin (diferuloylmethane), a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in human articular chondrocytes maintained in vitro. The effects of curcumin were studied in cultures of human articular chondrocytes treated with IL-1beta and TNF-alpha for up to 72h. Expression of collagen type II, integrin beta1, cyclo-oxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) was monitored by western blotting. The effects of curcumin on the expression, phosphorylation and nuclear translocation of protein components of the NF-kappaB system were studied by western blotting and immunofluorescence, respectively. Treatment of chondrocytes with curcumin suppressed IL-1beta-induced NF-kappaB activation via inhibition of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation and p65 nuclear translocation. Curcumin inhibited the IL-1beta-induced stimulation of up-stream protein kinase B Akt. These events correlated with down-regulation of NF-kappaB targets including COX-2 and MMP-9. Similar results were obtained in chondrocytes stimulated with TNF-alpha. Curcumin also reversed the IL-1beta-induced down-regulation of collagen type II and beta1-integrin receptor expression. These results indicate that curcumin has nutritional potential as a naturally occurring anti-inflammatory agent for treating OA through suppression of NF-kappaB mediated IL-1beta/TNF-alpha catabolic signalling pathways in chondrocytes.

Item Type: Article
Authors :
NameEmailORCID
Shakibaei, MUNSPECIFIEDUNSPECIFIED
John, TUNSPECIFIEDUNSPECIFIED
Schulze-Tanzil, GUNSPECIFIEDUNSPECIFIED
Lehmann, IUNSPECIFIEDUNSPECIFIED
Mobasheri, Aa.mobasheri@surrey.ac.ukUNSPECIFIED
Date : 1 May 2007
Identification Number : 10.1016/j.bcp.2007.01.005
Uncontrolled Keywords : Biological Transport, Cell Nucleus, Chondrocytes, Curcumin, Cyclooxygenase 2, Down-Regulation, Gene Expression Regulation, Humans, Interleukin-1beta, Matrix Metalloproteinase 9, Membrane Proteins, NF-kappa B, Oncogene Protein v-akt, Osteoarthritis, Phosphorylation, Signal Transduction, Synaptotagmin I, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Up-Regulation
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:12
Last Modified : 17 May 2017 14:47
URI: http://epubs.surrey.ac.uk/id/eprint/826815

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