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Titanium particles modulate expression of Toll‐like receptor proteins
Author(s) -
Pajarinen Jukka,
Mackiewicz Zygmunt,
Pöllänen Raimo,
Takagi Michiaki,
Epstein Noah J.,
Ma Ting,
Goodman Stuart B.,
Konttinen Yrjö T.
Publication year - 2009
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32495
Subject(s) - downregulation and upregulation , tlr2 , inflammation , tlr4 , receptor , toll like receptor , materials science , microbiology and biotechnology , titanium , biology , immunology , innate immune system , gene , biochemistry , metallurgy
The role of Toll‐like receptors (TLRs) responding to microbial remnants, indolent biofilms or cellular byproducts in aseptic loosening of joint replacements is unknown. Thus, the effect of titanium (Ti) particles on TLR protein levels was evaluated. To create a model of particle‐induced inflammation, an intramedullary stainless steel rod with and without Ti particles was bilaterally placed in the femora of 14 mice. The animals were sacrificed at 2 or 10 weeks postoperatively and paraffin‐embedded femur sections were evaluated for TLR1, 2, 4, 5, 8, and 9 proteins using immunohistochemistry. Decrease in the number of TLR immunoreactive cells was observed between weeks 2 and 10 in both settings. Furthermore, in the presence of Ti particles, the numbers of TLR immunoreactive cells were lower than in the presence of rod only at both time points, suggesting downregulation of TLR expression by Ti‐particles per se . Accordingly, in a short‐term 24 h stimulation, downregulation of TLR4 mRNA ( p < 0.02) was observed in vitro in RAW 264.7 cells challenged with Ti particles. Results suggest that after an initial inflammatory stage, TLRs are downregulated in response to Ti particles, possibly to inhibit excessive inflammation, although TLR downregulation might at the same time render tissues more susceptible to pathogens. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010