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

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.

journal_name

Ann N Y Acad Sci

authors

Minematsu H,Shin MJ,Celil Aydemir AB,Seo SW,Kim DW,Blaine TA,Macián F,Yang J,Lee FY

doi

10.1196/annals.1402.026

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

143-50

eissn

0077-8923

issn

1749-6632

pii

annals.1402.026

journal_volume

1117

pub_type

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