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

Abstract

Pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) 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-1β and TNF-α signalling pathways in human articular chondrocytes maintained in vitro. The effects of curcumin were studied in cultures of human articular chondrocytes treated with IL-1β and TNF-α for up to 72 h. Expression of collagen type II, integrin β1, 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-κB system were studied by western blotting and immunofluorescence, respectively. Treatment of chondrocytes with curcumin suppressed IL-1β-induced NF-κB activation via inhibition of IκBα phosphorylation, IκBα degradation, p65 phosphorylation and p65 nuclear translocation. Curcumin inhibited the IL-1β-induced stimulation of up-stream protein kinase B Akt. These events correlated with down-regulation of NF-κB targets including COX-2 and MMP-9. Similar results were obtained in chondrocytes stimulated with TNF-α. Curcumin also reversed the IL-1β-induced down-regulation of collagen type II and β1-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-κB mediated IL-1β/TNF-α catabolic signalling pathways in chondrocytes. © 2007 Elsevier Inc. All rights reserved.