Titanium particles modulate expression of Toll-like receptor proteins

Titanium particles modulate expression of Toll-like receptor proteins
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DOI:
10.1002/jbm.a.32495
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发表时间:
2010-03-15
影响因子:
4.9
通讯作者:
Konttinen, Yrjo T.
Konttinen, Yrjo T.
中科院分区:
工程技术3区
文献类型:
--
作者:
Pajarinen, Jukka;Mackiewicz, Zygmunt;Konttinen, Yrjo T.

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Toll样受体(TLR)对微生物残留物、惰性生物膜或细胞副产物的反应在关节置换物无菌性松动中的作用尚不清楚。因此,评价了钛(Ti)颗粒对TLR蛋白水平的影响。为了建立颗粒诱导的炎症模型,将含和不含钛颗粒的髓内不锈钢棒双侧放置在14只小鼠的股骨中。在术后2周或10周处死动物,并使用免疫组织化学评价石蜡包埋的股骨切片的TLR 1、2、4、5、8和9蛋白。在两种情况下,在第2周和第10周之间观察到TLR免疫反应细胞数量减少。此外,在存在钛颗粒的情况下,TLR免疫反应性细胞的数量在两个时间点均低于仅存在杆的情况,表明钛颗粒本身下调TLR表达。因此,在短期24小时刺激中,在体外用Ti颗粒攻击的RAW 264.7细胞中观察到TLR 4 mRNA的下调(p < 0.02)。结果表明,在初始炎症阶段后,TLR响应于Ti颗粒而下调,可能抑制过度炎症,尽管TLR下调可能同时使组织对病原体更敏感。(C)2009 Wiley Periodicals,Inc. J Biomed Mater Res 92A:1528- 1537,2010
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. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 92A: 1528-1537,2010