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Inhibition of Titanium Particle-Induced Inflammation by the Proteasome Inhibitor Bortezomib in Murine Macrophage-Like RAW 264.7 Cells

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Abstract

Wear particle-induced inflammatory osteolysis is the major cause of aseptic loosening after total joint replacement. The predominant cell type within periprosthetic tissues is macrophages. We investigate the anti-inflammatory effects of the proteasome inhibitor bortezomib (Bzb) on murine macrophage-like RAW 264.7 cells stimulated with titanium (Ti) particles. RAW 264.7 cells were cultured with 1 nM Bzb and 0.1 mg/ml Ti particles for 48 h; cells without Ti and Bzb or without Bzb were used as negative and loading controls. Results showed that the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10), chemokines [monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1α)], and inflammatory enzymes [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)] increased in RAW 264.7 cells cultured with Ti. Bzb treatment significantly reduced the expression of TNF-α, IL-1β, IL-6, MCP-1, MIP-1α, iNOS, and COX-2 and induced the expression of IL-10 in a time-dependent manner. These results suggest that Bzb inhibits Ti-induced inflammation in macrophages, and provide a promising therapeutic target for treating or preventing aseptic loosening.

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ACKNOWLEDGMENTS

This work was supported by the National Natural Science Foundation of China (NSFC, no. 81171688) and the Integration of Medicine and Engineering Foundation of Shanghai Jiaotong University (YG2010MS33).

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Authors and Affiliations

  1. Department of Orthopaedics, The Sixth Affiliated People’s Hospital, Shanghai Jiaotong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China

    Xin Mao, Xiaoyun Pan, Xiaochun Peng, Tao Cheng & Xianlong Zhang

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Correspondence to Xianlong Zhang.

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Mao, X., Pan, X., Peng, X. et al. Inhibition of Titanium Particle-Induced Inflammation by the Proteasome Inhibitor Bortezomib in Murine Macrophage-Like RAW 264.7 Cells. Inflammation 35, 1411–1418 (2012). https://doi.org/10.1007/s10753-012-9454-5

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