In end-stage arthritis patients total joint replacement is a very effective surgical procedure. macrophage cell line bone marrow derived macrophages and human THP1 macrophage cell line were suppressed by double strand decoy oligodeoxynucleotide (ODN) Epothilone B (EPO906) containing an NF-κB binding element. Macrophages exposure to UHMWPE particles with or without endotoxin induced pro-inflammatory cytokine and chemokine expression including TNF-α MCP1 MIP1α and others. Finally the decoy ODN significantly suppressed the induced cytokine and chemokine expression in both murine and human macrophages consequently reducing macrophage recruitment by cellular conditioned medium exposed to wear particles. These findings suggest that local suppression of inflammatory cytokine production via inhibition of NF-κB activity with decoy ODN in total joint replacement patients could potentially be an effective strategy to alleviate wear particle-induced chronic inflammation. Keywords: wear particles macrophage NF-κB decoy oligodeoxynucleotide periprosthetic osteolysis In end-stage arthritis patients total joint replacement is a highly successful surgical procedure. The revision rate (i.e. the rate of needing another Epothilone B (EPO906) operation for prosthesis failure) after TJR is around 10% and the revision procedure is more complicated with more bone loss and a poorer prognosis than the first surgery. Reducing the revision rate and limiting bone loss become prominent issues especially as TJR has been extended to younger patients. The generation of wear particles from implanted device for joint replacement is inevitable. Wear particles can be recognized by infiltrated immune cells including macrophages and secrete pro-inflammatory cytokines [1]. Blocking of individual cytokines via neutralizing antibody did not mitigate osteolysis in patients [2]. Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) is a key transcription factor that plays an essential role in the inflammatory response [3]. Targeting NF-κB activity via competitive binding Epothilone B (EPO906) with double strand decoy oligodeoxynucleotide (ODN) containing NF-κB binding element has been applied to many inflammatory disorders[4]. In our recent report “Suppression of wear particle induced pro-inflammatory cytokine and chemokine production in macrophages via NF-κB decoy oligodeoxynucleotide: A preliminary report” we investigated how NF-κB signaling play a role in the wear particle-mediated inflammatory response [5]. Wear particles induced NF-κB activation and pro-inflammatory cytokines expression in macrophages Ultra-High Molecular-Weight PolyEthylene (UHMWPE) wear particles (1.0 ± 0.1 μm) were used in this study. Mouse macrophage Natural264.7 NF-κB reporter cell clone was generated by stably transfecting the luciferase expression vector controlled by NF-κB response elements. Macrophages exposed to UHMWPE particles directly enhanced NF-κB activity by 50%. Mouse bone marrow derived macrophages and human being macrophage THP1 cells exposed to UHMWPE particles with or without endotoxin (1 μg/ml lipopolysaccharide) showed significant induction of multiple chemokine and cytokine manifestation including MCP1 MIP1α (macrophage attractant UTY chemokines) IL-8 CXCL1 (neutrophil attractant chemokines) TNFα and Epothilone B (EPO906) IL-1β (pro-inflammatory cytokines). Induction of MCP1 enhanced additional macrophage migration at later on time points (cells were exposed to the particles for 24 and 48 hrs). NF-κB decoy oligodeoxynucleotide suppressed put on particles induced cytokine manifestation and cellular migration in macrophages NF-κB decoy ODN (0.5 μM) was used to suppress the NF-κB activation in macrophages induced by UHMWPE particles or endotoxin. Interestingly naked decoy ODN shown the most efficient suppression of TNFα manifestation induced by endotoxin and NF-κB activation induced by put on particles in RAW264.7 cells. Next NF-κB decoy ODN suppressed the manifestation of multiple cytokines and chemokines including MCP1 MIP1α MIP1β IL-8 CXCL1 TNFα IL-1β and IL-6 at numerous levels which were shown in mouse bone marrow derived macrophages and human being macrophage THP1 cells exposed to UHMWPE particles with or without endotoxin. Finally induction of macrophage migration from the conditioned press exposed to put on particles with or without endotoxin was also reduced in NF-κB decoy ODN-treated cells. Tasks.