Faculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE1 4HH, UK.
Musculoskeletal Unit, Department of Orthopaedics, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK.
Sci Rep. 2021 May 18;11(1):10531. doi: 10.1038/s41598-021-89329-7.
Ceramic orthopaedic implants are increasingly popular due to the need for robust total joint replacement implants that have a high success rate long-term and do not induce biological responses in patients. This study was designed to investigate the biological effects of ceramic nanopowders containing aluminium oxide or zirconium oxide to activate the human macrophage THP-1 cell line. In vitro investigation of pro-inflammatory gene expression and chemokine secretion was performed studied using RT-qPCR and ELISA, respectively. TLR4 inhibition, using a small-molecule inhibitor, was used to determine whether ceramic-mediated inflammation occurs in a similar manner to that of metals such as cobalt. THP-1 macrophages were primed with ceramics or LPS and then treated with ATP or ceramics, respectively, to determine whether these nanopowders are involved in the priming or activation of the NLRP3 inflammasome through IL-1β secretion. Cells treated with ceramics significantly increased pro-inflammatory gene expression and protein secretion which was attenuated through TLR4 blockade. Addition of ATP to cells following ceramic treatment significantly increased IL-1β secretion. Therefore, we identify the ability of ceramic metal oxides to cause a pro-inflammatory phenotype in THP-1 macrophages and propose the mechanism by which this occurs is primarily via the TLR4 pathway which contributes to inflammasome signalling.
陶瓷骨科植入物由于需要具有高成功率和长期效果的坚固的全关节置换植入物,并且不会在患者中引起生物反应,因此越来越受欢迎。本研究旨在研究含有氧化铝或氧化锆的陶瓷纳米粉末对人巨噬细胞 THP-1 细胞系的生物学效应。通过 RT-qPCR 和 ELISA 分别研究了促炎基因表达和趋化因子分泌的体外研究。使用小分子抑制剂抑制 TLR4 ,以确定陶瓷介导的炎症是否以类似于金属(如钴)的方式发生。用陶瓷或 LPS 预刺激 THP-1 巨噬细胞,然后分别用 ATP 或陶瓷处理,以确定这些纳米粉末是否通过 IL-1β 分泌参与 NLRP3 炎性小体的启动或激活。用陶瓷处理的细胞显著增加了促炎基因表达和蛋白分泌,通过 TLR4 阻断可减弱该作用。陶瓷处理后添加 ATP 可显著增加 IL-1β 的分泌。因此,我们确定了陶瓷金属氧化物在 THP-1 巨噬细胞中引起促炎表型的能力,并提出了这种作用发生的机制主要是通过 TLR4 途径,该途径有助于炎性小体信号传导。