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- Title
Orthopedic implant particle-induced tumor necrosis factor-alpha production in macrophage-monocyte lineage cells is mediated by nuclear factor of activated T cells.
- Authors
Minematsu, Hiroshi; Shin, Mike J; Celil Aydemir, Ayse B; Seo, Sung Wook; Kim, Dae Won; Blaine, Theodore A; Macián, Fernando; Yang, Jay; Lee, Francis Young
- Abstract
Wear particles produced from artificial joint prostheses are known to cause macrophage-monocyte lineage cells to produce proosteoclastogenic cytokines, including tumor necrosis factor (TNF)-alpha. The specific molecular mechanism, however, is not yet known. Bioinformatic analysis showed that the promoter region of TNF-alpha has several consensus sequences for NFAT binding. Consequently, we examined the role of nuclear factor of activated T cells (NFAT) in TNF-alpha production. Our investigation has shown that treatment with titanium nanoparticles increased TNF-alpha gene expression along with TNF-alpha protein secretion in murine macrophage-like RAW264.7 and primary monocyte-macrophage cells. Titanium particle-induced TNF-alpha induction was inhibited by VIVIT, a peptide inhibitor that targets the calcineurin/NFAT axis, which suggests that NFAT mediates metallic particle-induced TNF-alpha expression in monocyte-macrophage lineage cells.
- Publication
Annals of the New York Academy of Sciences, 2007, Vol 1117, p143
- ISSN
0077-8923
- Publication type
Journal Article
- DOI
10.1196/annals.1402.026