Galli Marco, Toriani Terenzi Caterina, Falcone Gianluca, Pozzetto Ubaldo, Tringali Giuseppe, De Santis Vincenzo, Vairano Mauro, Navarra Pierluigi, Pozzoli Giacomo
Institute of Orthopedics, Catholic University School of Medicine, 00168 Rome, Italy.
Int J Mol Med. 2006 Jul;18(1):141-5.
In this study the potential of clinically relevant alumina ceramic and metal wear particles to induce an in vitro inflammatory response was assessed in human monocytes and lymphocytes isolated from healthy donors by measuring prostaglandin E2 (PGE2) levels and mRNA expression of various pro-inflammatory cytokines. Bacterial lipopolysaccharide (LPS) was used as positive control. LPS significantly increased PGE2 levels in the incubation medium of monocyte cultures after 24 h. Alumina had no effect on PGE2 production, whereas metals induced a concentration-dependent increase in PGE2 release, that was statistically significant at the dose of 0.1 mg/ml. In lymphocytes, LPS elicited a weak but significant increase in PGE2 release, whereas both alumina and metals did not modify PGE2 amounts at any of the concentrations tested. The gene expression of a number of pro- and anti-inflammatory cytokines was assessed in monocytes and lymphocytes exposed to LPS, 0.1 mg/ml alumina or 0.1 mg/ml metals for 24 h. In monocytes, LPS caused a 2-fold increase in interleukin-1beta (IL-1beta) mRNA levels. The exposure of monocytes to metals resulted in a selective increase in IL-1beta mRNA accumulation (+48% compared to control). By contrast, alumina did not modify IL-1beta mRNA levels. None of the test substances elicited any response on purified lymphocyte population. These findings suggest that PGE2 production and IL-1 mRNA expression are a reliable marker to study the pro-inflammatory effects of wear debris in vitro. The lower activity of alumina compared to metals suggests that the former should be preferred in implants for its favorable biological and mechanical behavior.
在本研究中，通过测量前列腺素E2（PGE2）水平以及多种促炎细胞因子的mRNA表达，评估了具有临床相关性的氧化铝陶瓷和金属磨损颗粒在体外诱导从健康供体分离出的人单核细胞和淋巴细胞产生炎症反应的潜力。细菌脂多糖（LPS）用作阳性对照。24小时后，LPS显著增加了单核细胞培养物孵育培养基中的PGE2水平。氧化铝对PGE2的产生没有影响，而金属则诱导PGE2释放呈浓度依赖性增加，在剂量为0.1mg/ml时具有统计学意义。在淋巴细胞中，LPS引起PGE2释放微弱但显著增加，而氧化铝和金属在任何测试浓度下均未改变PGE2的量。评估了暴露于LPS、0.1mg/ml氧化铝或0.1mg/ml金属24小时的单核细胞和淋巴细胞中多种促炎和抗炎细胞因子的基因表达。在单核细胞中，LPS使白细胞介素-1β（IL-1β）mRNA水平增加了2倍。单核细胞暴露于金属导致IL-1βmRNA积累选择性增加（与对照相比增加48%）。相比之下，氧化铝未改变IL-1βmRNA水平。没有一种测试物质对纯化的淋巴细胞群体产生任何反应。这些发现表明，PGE2的产生和IL-1 mRNA表达是体外研究磨损碎片促炎作用的可靠标志物。与金属相比，氧化铝的活性较低，这表明由于其良好的生物学和力学行为，前者在植入物中应更受青睐。
