Effects of Curcumin (Diferuloylmethane) on Nuclear Factor κB Signaling in Interleukin‐1β‐Stimulated Chondrocytes

Abstract

A bstract: 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.