Suppression of NF-κB 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

Pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-a (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 CA 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-1 beta 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-1 beta and TNF-alpha for up to 72 h. Expression of collagen type II, integrin beta 1, cyclooxygenase-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-kappa B system were studied by western blotting and immunofluorescence, respectively. Treatment of chondrocytes with curcumin suppressed IL-1 beta-induced NF-kappa B activation via inhibition of I kappa B alpha phosphorylation, I kappa B alpha degradation, p65 phosphorylation and p65 nuclear translocation. Curcumin inhibited the IL-1 beta-induced stimulation of up-stream protein kinase B Akt. These events correlated with down-regulation of NF-kappa B targets including COX-2 and MMP-9. Similar results were obtained in chondrocytes stimulated with TNF-alpha. Curcumin also reversed the IL-1 beta-induced down-regulation of Collagen type II and beta 1-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-kappa B mediated IL-1 beta/TNF-alpha catabolic signalling pathways in chondrocytes. (c) 2007 Elsevier Inc. All rights reserved.