Wear particles promote endotoxin tolerance in macrophages by inducing interleukin-1 receptor-associated kinase-M expression.
Wear particles promote endotoxin tolerance in macrophages by inducing interleukin-1 receptor-associated kinase-M expression.
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DOI：
10.1002/jbm.a.34375
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发表时间：
2013-03
期刊：
影响因子：
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通讯作者：
Yangchun Zhang;Shiming Yu;Jianhong Xiao;C. Hou;Ziqing Li;Ziji Zhang;Qiyi Zhai;M. Lehto;Y. Konttinen;P. Sheng
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文献类型：
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作者：
Yangchun Zhang;Shiming Yu;Jianhong Xiao;C. Hou;Ziqing Li;Ziji Zhang;Qiyi Zhai;M. Lehto;Y. Konttinen;P. Sheng
识别病原体相关分子模式（PAMP）的Toll样受体（TLR）在局部免疫中发挥作用，并参与种植体相关松动。TLR介导的信号传导受白细胞介素-1受体相关激酶-M（IRAK-M）调节。我们以前的研究已经证明IRAK-M是由假体周围组织巨噬细胞中的磨损颗粒诱导的。本研究通过脂多糖（LPS）和/或钛（Ti）颗粒刺激以及小干扰RNA（siRNA）进一步探讨IRAK-M的相关机制。免疫印迹法检测IRAK-M蛋白表达水平，ELISA法检测肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1β）水平。结果表明，钛颗粒预处理后，LPS刺激RAW264.7细胞，IRAK-M与LPS刺激相比变化不大。Ti颗粒预暴露后，先用LPS刺激培养细胞，TNF-α和IL-1β水平低于LPS加Ti颗粒和不加Ti颗粒刺激培养细胞（p0.05）。细胞因子在单独的Ti颗粒刺激中最低。siRNA沉默后，IRAK-M缺陷细胞在Ti颗粒预暴露后和单独用Ti颗粒刺激时，在LPS刺激中表现出细胞因子表达增加。我们的研究结果表明，碎片诱导的IRAK-M减少了异物反应，但同时，IRAK-M的过度表达也可能不利于PAMP或细菌的局部侵入，负调节LPS诱导和TLR介导的炎症，并导致假体周围组织的免疫抑制，这可能易患植入物相关感染。
Toll-like receptors (TLRs) recognizing pathogen-associated molecular patterns (PAMP) play a role in local immunity and participate in implant-associated loosening. TLRs-mediated signaling is regulated by interleukin-1 receptor-associated kinase-M (IRAK-M). Our previous studies have proved that IRAK-M is induced by wear particles in macrophages from periprosthetic tissues. In this study, the IRAK-M-related mechanisms were further explored by lipopolysaccharide (LPS) and/or titanium (Ti) particles stimulations and small interfering RNAs (siRNAs). The protein level of IRAK-M was studied using western blotting and tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels were measured using ELISA. Results showed that in RAW264.7 cells stimulated by LPS after Ti particle pre-exposure, IRAK-M was slightly changed, compared with LPS stimulation. And levels of TNF-α and IL-1β in cultures stimulated by LPS first after Ti particle pre-exposure were lower than in the other two groups which were stimulated by LPS with or without Ti particles (p 0.05). The cytokines were lowest in Ti particles alone stimulation. After siRNAs silenced, IRAK-M-deficient cells exhibited increased expression of the cytokines in LPS stimulation after Ti particle pre-exposure and when stimulated with Ti particles alone. Our findings suggest that debris-induced IRAK-M decreases foreign body reactions, but at the same time, the over-expression of IRAK-M may also be detrimental on local intrusion of PAMPs or bacteria, negatively regulates the LPS-induced and TLRs-mediated inflammation and results in immunosuppression in periprosthetic tissue, which may predispose to implant-associated infections.