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Minematsu, H. et al.

Orthopedic implant particle-induced tumor necrosis factor-alpha production in macrophage-monocyte lineage cells is mediated by nuclear factor of activated T cells.

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.[1]

References

Orthopedic implant particle-induced tumor necrosis factor-alpha production in macrophage-monocyte lineage cells is mediated by nuclear factor of activated T cells. Minematsu, H., Shin, M.J., Celil Aydemir, A.B., Seo, S.W., Kim, D.W., Blaine, T.A., Macián, F., Yang, J., Young-In Lee, F. Ann. N. Y. Acad. Sci. (2007) [Pubmed]

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