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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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  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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