Effects of Curcumin (Diferuloylmethane) on Nuclear Factor κB Signaling in Interleukin-1β-Stimulated Chondrocytes
Article first published online: 12 JAN 2006
Annals of the New York Academy of Sciences
How to Cite
SCHULZE-TANZIL, G., MOBASHERI, A., SENDZIK, J., JOHN, T. and SHAKIBAEI, M. (2004), Effects of Curcumin (Diferuloylmethane) on Nuclear Factor κB Signaling in Interleukin-1β-Stimulated Chondrocytes. Annals of the New York Academy of Sciences, 1030: 578–586. doi: 10.1196/annals.1329.067
- Issue published online: 8 JUL 2009
- Article first published online: 12 JAN 2006
Abstract: Curcumin (diferuloylmethane) is a nontoxic dietary pigment in tumeric and curry and a potent inhibitor of the common transcription factor Nuclear Factor κB (NF-κB) in several cell types. It is well established that some of the catabolic effects of the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α in osteoarthritis are regulated by the activation of NF-κB. Therefore, the aim of this study was to determine whether curcumin modifies the catabolic response of chondrocytes to IL-1β. Human articular chondrocytes were prestimulated with 10 ng/mL IL-1β for 0, 4, 8, 12, or 24 h and then cotreated with 50 μM curcumin for 0, 12, 24, 36, or 48 h. Synthesis of the cartilage-specific collagen type II and matrix-degrading enzyme matrix metalloproteinase-3 (MMP-3) was investigated in chondrocytes by Western blot analysis. Activation and nuclear translocation of NF-κB were observed by immunofluorescence microscopy. IL-1β induced a decrease in collagen type II and upregulation of MMP-3 in a time-dependent manner. Upregulation of MMP-3 was inhibited by curcumin in a time-dependent manner. In addition, IL-1β-induced a decrease in type II collagen, which was relieved by curcumin treatment. In response to IL-1β, NF-κB translocated to the nucleus, but translocation was inhibited by curcumin, as revealed by immunofluorescence microscopy. Taken together, these results confirmed an IL-1β-mediated upregulation of proinflammatory MMP-3 in chondrocytes via an NF-κB activation mechanism. Curcumin protected chondrocytes from the catabolic effects of IL-1β, such as MMP-3 upregulation, and interestingly also relieved cytokine-induced suppression of matrix protein synthesis. Therefore, curcumin antagonizes crucial catabolic effects of IL-1β signaling that are known to contribute to the pathogenesis of osteoarthritis.