PMID- 15659840 OWN - NLM STAT- MEDLINE DCOM- 20050616 LR - 20240109 IS - 0077-8923 (Print) IS - 0077-8923 (Linking) VI - 1030 DP - 2004 Dec TI - Effects of curcumin (diferuloylmethane) on nuclear factor kappaB signaling in interleukin-1beta-stimulated chondrocytes. PG - 578-86 AB - Curcumin (diferuloylmethane) is a nontoxic dietary pigment in tumeric and curry and a potent inhibitor of the common transcription factor Nuclear Factor kappaB (NF-kappaB) in several cell types. It is well established that some of the catabolic effects of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha in osteoarthritis are regulated by the activation of NF-kappaB. Therefore, the aim of this study was to determine whether curcumin modifies the catabolic response of chondrocytes to IL-1beta. Human articular chondrocytes were prestimulated with 10 ng/mL IL-1beta for 0, 4, 8, 12, or 24 h and then cotreated with 50 microM 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-kappaB were observed by immunofluorescence microscopy. IL-1beta 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-1beta-induced a decrease in type II collagen, which was relieved by curcumin treatment. In response to IL-1beta, NF-kappaB translocated to the nucleus, but translocation was inhibited by curcumin, as revealed by immunofluorescence microscopy. Taken together, these results confirmed an IL-1beta-mediated upregulation of proinflammatory MMP-3 in chondrocytes via an NF-kappaB activation mechanism. Curcumin protected chondrocytes from the catabolic effects of IL-1beta, such as MMP-3 upregulation, and interestingly also relieved cytokine-induced suppression of matrix protein synthesis. Therefore, curcumin antagonizes crucial catabolic effects of IL-1beta signaling that are known to contribute to the pathogenesis of osteoarthritis. FAU - Schulze-Tanzil, Gundula AU - Schulze-Tanzil G AD - Charite University Medical School Berlin, Institute of Anatomy, Department of Cell and Neurobiology, Campus Benjamin Franklin, Konigin-Luise-Strasse 15, D-14195 Berlin, Germany. FAU - Mobasheri, Ali AU - Mobasheri A FAU - Sendzik, Judith AU - Sendzik J FAU - John, Thilo AU - John T FAU - Shakibaei, Mehdi AU - Shakibaei M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Interleukin-1) RN - 0 (NF-kappa B) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - IT942ZTH98 (Curcumin) SB - IM MH - Blotting, Western MH - Cartilage, Articular/cytology/*drug effects/enzymology/metabolism MH - Cell Nucleus/metabolism MH - Cells, Cultured MH - Chondrocytes/*drug effects/enzymology/metabolism MH - Collagen/metabolism MH - Curcumin/*pharmacology MH - Humans MH - Interleukin-1/*pharmacology MH - Matrix Metalloproteinase 3/metabolism MH - Microscopy, Fluorescence MH - NF-kappa B/*metabolism MH - Signal Transduction/*drug effects EDAT- 2005/01/22 09:00 MHDA- 2005/06/17 09:00 CRDT- 2005/01/22 09:00 PHST- 2005/01/22 09:00 [pubmed] PHST- 2005/06/17 09:00 [medline] PHST- 2005/01/22 09:00 [entrez] AID - 1030/1/578 [pii] AID - 10.1196/annals.1329.067 [doi] PST - ppublish SO - Ann N Y Acad Sci. 2004 Dec;1030:578-86. doi: 10.1196/annals.1329.067.