Effects of interleukin-10 on titanium particle-induced macrophage transcription factor activation and cytokine...

This study tests the hypothesis that transcription factor activation by exposure of macrophages to titanium particles can be modulated by the addition of the antiinflammatory cytokine, interleukin 10 (IL-10). The experiments were carried out with primary human monocyte/macrophages that were treated in the presence or absence of IL-10 with and without exposure to titanium particles. The time course for experiments varied from 1 h-5 h for analysis of nuclear protein and up to 48 h for analysis of cytokine release. Transcription factor translocation to the nucleus was analyzed using electrophoretic gel shift assays and cytokine release was quantified by enzyme-linked immunosorbent assay. Addition of titanium particles increased release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta). In addition, titantium particle induced translocation of the transcription factors, NF-kappa B and NF-IL6, in the nucleus within 1 h. Treatment of macrophages with IL-10 prior to exposure to titanium particles decreased translocation of NF-IL6 but did not significantly alter nuclear levels of NF-kappa B. In addition, pretreatment of the cells with IL-10 decreased particle-induced cytokine release. These data show that antiinflammatory cytokines may provide a mechanism by which particle-induced inflammatory response may be modulated in vivo.