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Orthopedic Implant Particle‐Induced Tumor Necrosis Factor‐α Production in Macrophage–Monocyte Lineage Cells Is Mediated by Nuclear Factor of Activated T Cells
Author(s) -
MINEMATSU HIROSHI,
SHIN MIKE J.,
CELIL AYDEMIR AYSE B.,
SEO SUNG WOOK,
KIM DAE WON,
BLAINE THEODORE A.,
MACIÁN FERNANDO,
YANG JAY,
YOUNGIN LEE FRANCIS
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.026
Subject(s) - nfat , tumor necrosis factor alpha , monocyte , macrophage , microbiology and biotechnology , biology , cancer research , chemistry , immunology , transcription factor , biochemistry , gene , in vitro
: Wear particles produced from artificial joint prostheses are known to cause macrophage–monocyte lineage cells to produce proosteoclastogenic cytokines, including tumor necrosis factor (TNF)‐α. The specific molecular mechanism, however, is not yet known. Bioinformatic analysis showed that the promoter region of TNF‐α has several consensus sequences for NFAT binding. Consequently, we examined the role of nuclear factor of activated T cells (NFAT) in TNF‐α production. Our investigation has shown that treatment with titanium nanoparticles increased TNF‐α gene expression along with TNF‐α protein secretion in murine macrophage‐like RAW264.7 and primary monocyte–macrophage cells. Titanium particle‐induced TNF‐α induction was inhibited by VIVIT, a peptide inhibitor that targets the calcineurin/NFAT axis, which suggests that NFAT mediates metallic particle‐induced TNF‐α expression in monocyte–macrophage lineage cells.