Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19449-54. doi: 10.1073/pnas.1008155107. Epub 2010 Oct 25.
Nanoparticles are increasingly used in various fields, including biomedicine and electronics. One application utilizes the opacifying effect of nano-TiO(2), which is frequently used as pigment in cosmetics. Although TiO(2) is believed to be biologically inert, an emerging literature reports increased incidence of respiratory diseases in people exposed to TiO(2). Here, we show that nano-TiO(2) and nano-SiO(2), but not nano-ZnO, activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome, leading to IL-1β release and in addition, induce the regulated release of IL-1α. Unlike other particulate Nlrp3 agonists, nano-TiO(2)-dependent-Nlrp3 activity does not require cytoskeleton-dependent phagocytosis and induces IL-1α/β secretion in nonphagocytic keratinocytes. Inhalation of nano-TiO(2) provokes lung inflammation which is strongly suppressed in IL-1R- and IL-1α-deficient mice. Thus, the inflammation caused by nano-TiO(2) in vivo is largely caused by the biological effect of IL-1α. The current use of nano-TiO(2) may present a health hazard due to its capacity to induce IL-1R signaling, a situation reminiscent of inflammation provoked by asbestos exposure.
纳米颗粒在包括生物医药和电子学在内的各个领域的应用日益广泛。其中一种应用是利用纳米 TiO(2) 的光学不透明性，纳米 TiO(2) 常被用作化妆品中的颜料。尽管 TiO(2) 被认为具有生物惰性，但新兴文献报告称，接触 TiO(2) 的人群中呼吸道疾病的发病率增加。在这里，我们表明纳米 TiO(2) 和纳米 SiO(2)，但不是纳米 ZnO，可激活 NLR 含 pyrin 结构域蛋白 3（Nlrp3）炎性小体，导致 IL-1β 的释放，并可诱导 IL-1α 的调节性释放。与其他颗粒状 Nlrp3 激动剂不同，纳米 TiO(2) 依赖性 Nlrp3 活性不需要细胞骨架依赖性吞噬作用，并且在非吞噬角质形成细胞中诱导 IL-1α/β 的分泌。吸入纳米 TiO(2) 会引发肺部炎症，而在缺乏 IL-1R 和 IL-1α 的小鼠中，这种炎症会被强烈抑制。因此，体内纳米 TiO(2) 引起的炎症在很大程度上是由 IL-1α 的生物学效应引起的。由于纳米 TiO(2) 具有诱导 IL-1R 信号的能力，其当前的用途可能会带来健康危害，这种情况让人联想到暴露于石棉引起的炎症。
