title: Inhibition of titanium particle-induced inflammation by the proteasome inhibitor bortezomib in murine macrophage-like RAW 264.7 cells.
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-1 alpha (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.
authors.affiliation: Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Mao
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pan
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Peng
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Xianlong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D016753:Interleukin-10 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D014025:Titanium / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001897:Boronic Acids; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D061988:Proteasome Inhibitors; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000069286:Bortezomib; D014025:Titanium; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2