PMID- 22427154 OWN - NLM STAT- MEDLINE DCOM- 20130130 LR - 20211021 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 35 IP - 4 DP - 2012 Aug TI - Inhibition of titanium particle-induced inflammation by the proteasome inhibitor bortezomib in murine macrophage-like RAW 264.7 cells. PG - 1411-8 LID - 10.1007/s10753-012-9454-5 [doi] AB - 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-alpha, IL-1beta, IL-6, and IL-10), chemokines [monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1alpha)], 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-alpha, IL-1beta, IL-6, MCP-1, MIP-1alpha, 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. FAU - Mao, Xin AU - Mao X AD - Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China. FAU - Pan, Xiaoyun AU - Pan X FAU - Peng, Xiaochun AU - Peng X FAU - Cheng, Tao AU - Cheng T FAU - Zhang, Xianlong AU - Zhang X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Boronic Acids) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Proteasome Inhibitors) RN - 0 (Pyrazines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 69G8BD63PP (Bortezomib) RN - D1JT611TNE (Titanium) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.1 (Cyclooxygenase 2) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/pharmacology MH - Boronic Acids/*pharmacology MH - Bortezomib MH - Cell Line MH - Cell Survival/drug effects MH - Chemokine CCL2/biosynthesis MH - Cyclooxygenase 2/biosynthesis MH - Inflammation/chemically induced/*drug therapy MH - Interleukin-10/biosynthesis MH - Interleukin-1beta/biosynthesis/drug effects MH - Interleukin-6/biosynthesis MH - Macrophage Inflammatory Proteins/biosynthesis MH - Macrophages/*drug effects/immunology/metabolism MH - Mice MH - Nitric Oxide Synthase Type II/biosynthesis MH - Proteasome Inhibitors/*pharmacology MH - Pyrazines/*pharmacology MH - Titanium/*pharmacology MH - Tumor Necrosis Factor-alpha/biosynthesis/drug effects EDAT- 2012/03/20 06:00 MHDA- 2013/01/31 06:00 CRDT- 2012/03/20 06:00 PHST- 2012/03/20 06:00 [entrez] PHST- 2012/03/20 06:00 [pubmed] PHST- 2013/01/31 06:00 [medline] AID - 10.1007/s10753-012-9454-5 [doi] PST - ppublish SO - Inflammation. 2012 Aug;35(4):1411-8. doi: 10.1007/s10753-012-9454-5.