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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.
Biochem Pharmacol. 2007 May 01; 73(9):1434-45.BP

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.

Authors+Show Affiliations

Institute of Anatomy, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 11, D-80336 Munich, Germany. mehdi.shakibaei@med.uni-muenchen.deNo 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

17291458

Citation

Shakibaei, Mehdi, et al. "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." Biochemical Pharmacology, vol. 73, no. 9, 2007, pp. 1434-45.
Shakibaei M, John T, Schulze-Tanzil G, et al. 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. 2007;73(9):1434-45.
Shakibaei, M., John, T., Schulze-Tanzil, G., Lehmann, I., & 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. Biochemical Pharmacology, 73(9), 1434-45.
Shakibaei M, et al. 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. 2007 May 1;73(9):1434-45. PubMed PMID: 17291458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Shakibaei,Mehdi, AU - John,Thilo, AU - Schulze-Tanzil,Gundula, AU - Lehmann,Ingo, AU - Mobasheri,Ali, Y1 - 2007/01/07/ PY - 2006/09/14/received PY - 2006/11/22/revised PY - 2007/01/03/accepted PY - 2007/2/13/pubmed PY - 2007/5/18/medline PY - 2007/2/13/entrez SP - 1434 EP - 45 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 73 IS - 9 N2 - 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. SN - 0006-2952 UR - https://www.unboundmedicine.com/medline/citation/17291458/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(07)00014-7 DB - PRIME DP - Unbound Medicine ER -