期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 45, 页码 19449-19454出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1008155107
关键词
caspase-1; titanium dioxide; silica dioxide
资金
- Deutsche Forschungsgemeinschaft [YA-182/1-1]
Nanoparticles are increasingly used in various fields, including biomedicine and electronics. One application utilizes the opacifying effect of nano-TiO2, which is frequently used as pigment in cosmetics. Although TiO2 is believed to be biologically inert, an emerging literature reports increased incidence of respiratory diseases in people exposed to TiO2. Here, we show that nano-TiO2 and nano-SiO2, but not nano-ZnO, activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome, leading to IL-1 beta release and in addition, induce the regulated release of IL-1 alpha. Unlike other particulate Nlrp3 agonists, nano-TiO2-dependent-Nlrp3 activity does not require cytoskeleton-dependent phagocytosis and induces IL-1 alpha/beta secretion in nonphagocytic keratinocytes. Inhalation of nano-TiO2 provokes lung inflammation which is strongly suppressed in IL-1R- and IL-1 alpha-deficient mice. Thus, the inflammation caused by nano-TiO2 in vivo is largely caused by the biological effect of IL-1 alpha. The current use of nano-TiO2 may present a health hazard due to its capacity to induce IL-1R signaling, a situation reminiscent of inflammation provoked by asbestos exposure.
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