Titanium particles induce the immediate early stress responsive chemokines IL-8 and MCP-1 in osteoblasts

被引:61
作者
Fritz, EA
Glant, TT
Vermes, C
Jacobs, JJ
Roebuck, KA
机构
[1] Rush Univ, Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA
[2] Rush Univ, Rush Presbyterian St Lukes Med Ctr, Dept Biochem, Chicago, IL 60612 USA
[3] Rush Univ, Rush Presbyterian St Lukes Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA
关键词
chemokines; osteoblast; NF-kappa B; particulates; IL-8; MCP-1;
D O I
10.1016/S0736-0266(01)00154-1
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Exposure of human osteoblasts to ultrafine titanium (Ti) particles has been shown to alter osteoblast gene expression. We previously reported that Ti particles can increase IL-6 release and suppress the gene expression of procollagens alpha(1)[I] and alpha(2)[III] in human osteoblasts. In this study, we now demonstrate that Ti particles can rapidly induce the chemotactic cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1). two immediate early stress responsive chemokines important for the activation and chemotaxis of neutrophils and macrophages, respectively. In MG-63 osteosarcoma cells and bone marrow derived primary osteoblasts Ti particles selectively increased the steady state levels of IL-8 and MCP-1 mRNA in a time and concentration dependent manner. The increased chemokine mRNA correlated with increased secretion of IL-8 and MCP-1 protein. Actinomycin D, a potent RNA polymerase II inhibitor, blocked the Ti particle induction of IL-8 and MCP-1 mRNA expression, whereas cycloheximide. which inhibits protein synthesis, failed to inhibit chemokine gene expression suggesting Ti particles directly target activation of chemokine gene transcription. Consistent with a transcriptional mechanism not involving new protein synthesis, we demonstrate that Ti particles induce the binding of the p65 and p50 subunits of the latent transcription factor NF-kappaB to the IL-8 gene promoter. Taken together, these data demonstrate that Ti particles can activate transcription of the stress responsive chemokine genes IL-8 and MCP-1 in human osteoblasts. (C) 2002 Published by Elsevier Science Ltd. on behalf of Orthopaedic Research Society.
引用
收藏
页码:490 / 498
页数:9
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