The Research On The Inhibitive Function And Mechanism Of IL-37 In The Inflammatory Osteolysis Induced By Wear Particles

ObjectiveTo explore the effects of Interleukin (IL)-37 on wear-particle-induced periprosthetic osteolysis (WPO) and subsequent aseptic loosening, as well as the possible mechanisms.MethodsWe conducted a vitro experiment about titanium(Ti) particle induced inflammation system using RAW264.7 cells, which were then divided into three groups:control group, Ti group and IL-37+Ti group(Ti group pretreated with different levels of IL-37). IL-1β, IL-6, TNF-α were detected by ELISA. The mRNA of TGF-β, Caspase-1, NLRP3, IL-1β, IL-6, TNF-α were detected using PCR. We also applied Westernblot to observe p65、p38、ERK1/2、IL-6、TNF-α、pro-IL-1β, IL-1β, TGF-β, Caspase-1, p-p65 and phosphorylated p38 and ERK1/2.ResultsThe results of ELISA and RT-PCR showed:compared to the Ti group, the Caspase-1, NLRP3, IL-1β, IL-6, TNF-α of both control group and the IL-37+Ti group were significantly lower (p< 0.05), which especially decreased as the IL-37 concentration increase. The results of Westernblot consolidated similar results (p< 0.05).ConclusionBased on the results of our study, we conclude that Ti particles induced inflammation by up-regulating the expression of IL-1b, IL-6, TNF-α through NLRP3, MAPK, NF-κB pathways. IL-37 can inhibit the expression of Ti particles induced inflammatory factor IL-6, IL-1β, TNF-α by down-regulating NLRP3, MAPK, NF-κB pathways. IL-37 might be a potential novel therapeutic cytokine for WPO and subsequent aseptic loosening.