TLRs recognizing PAMPS play a role in local immunity and participate in implant-associated loosening. TLR-mediated signaling is primarily regulated by IL-1 receptor associated kinase-M (IRAK-M) negatively and IRAK-4 positively. Our previous studies have proved that wear particles promote endotoxin tolerance in macrophages by inducing IRAK-M. However, whether IRAK-4 is involved in inflammatory osteolysis of wear particles basically, and the specific mechanism of IRAK-4 around loosened hip implants, is still unclear. IRAK-4 was studied in the interface membranes from patients in vivo and in particle-stimulated macrophages to clarify its role. Also, IL-1β and TNF-α levels were measured after particle and LPS stimulation in macrophages with or without IRAK-4 silenced by siRNA. Our results showed that the interface membranes around aseptic and septic loosened prosthesis expressed more IRAK-4 compared with membranes from osteoarthritic patients. IRAK-4 in macrophages increased upon particle and LPS stimulation. In the former, IL-1β and TNF-α levels were lower compared with those of LPS stimulation, and IRAK-4 siRNA could suppress production of pro-inflammatory cytokines. These findings suggest that besides IRAK-M, IRAK-4 also plays an important role in the local inflammatory reaction and contributes to prosthesis loosening.

识别 PAMPS 的 TLR 在局部免疫中发挥作用，并参与与植入物相关的松动。TLR 介导的信号传导主要受 IL-1 受体相关激酶-M (IRAK-M) 的负向调节和 IRAK-4 的正向调节。我们之前的研究已经证明，磨损颗粒通过诱导 IRAK-M 来促进巨噬细胞对内毒素的耐受性。但 IRAK-4 是否基本参与磨损颗粒的炎症性骨溶解，以及 IRAK-4 围绕髋关节假体松动的具体机制尚不清楚。在体内患者的界面膜中研究了 IRAK-4并在粒子刺激的巨噬细胞中阐明其作用。此外，在有或没有被 siRNA 沉默的 IRAK-4 的情况下，在巨噬细胞中颗粒和 LPS 刺激后测量 IL-1β 和 TNF-α 水平。我们的研究结果表明，与骨关节炎患者的膜相比，无菌和脓毒性松动假体周围的界面膜表达更多的 IRAK-4。巨噬细胞中的 IRAK-4 在颗粒和 LPS 刺激下增加。前者，IL-1β和TNF-α水平低于LPS刺激，IRAK-4 siRNA可以抑制促炎细胞因子的产生。这些发现表明，除 IRAK-M 外，IRAK-4 在局部炎症反应中也起重要作用，并有助于假体松动。