2013年2月1日星期五

Inhibition of titanium particle-induced inflammation by the proteasome inhibitor bortezomib in murine macrophage-like RAW 264.7 cells.

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Inhibition of titanium particle-induced inflammation by the proteasome inhibitor bortezomib in murine macrophage-like RAW 264.7 cells.

Inflammation. 2012 Aug;35(4):1411-8

Authors: Mao X, Pan X, Peng X, Cheng T, Zhang X

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-?, IL-1?, IL-6, and IL-10), chemokines [monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1?)], 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-?, IL-1?, IL-6, MCP-1, MIP-1?, 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.

PMID: 22427154 [PubMed - indexed for MEDLINE]

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