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.
Center for Orthopedic Research, Department of Orthopedic Surgery, Columbia University, New York, NY 10032, USA.
Hiroshi
H
Minematsu
Mike J
MJ
Shin
Ayse B
AB
Celil Aydemir
Sung Wook
SW
Seo
Dae Won
DW
Kim
Theodore A
TA
Blaine
Fernando
F
Macián
Jay
J
Yang
Francis Young
FY
Lee
Francis
F
Young-In Lee
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002460:Cell Line; D019070:Cell Lineage; D019295:Computational Biology; D005786:Gene Expression Regulation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D009985:Orthopedics; D019736:Prostheses and Implants; D011485:Protein Binding; D014025:Titanium / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D050778:NFATC Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium; D019703:Calcineurin