Titanium dioxide induces different levels of IL-1β production dependent on its particle characteristics through caspase-1 activation mediated by reactive oxygen species and cathepsin B

Although titanium dioxide (TiO2) is widely used, its inhalation can induce inflammatory diseases accompanied by interleukin-1β (IL-1β) production. The particle characteristics of TiO2 are important factors in its biological effects. It is urgently necessary to investigate the relationship between the particle characteristics and biological responses for the development of safe forms of TiO2. Here, we systematically compared the production of IL-1β in response to various forms of TiO2 by macrophage-like human THP-1 cells using various sizes (nano to micro), crystal structures (anatase or rutile), and shapes (spherical or spicular) of TiO2. The production of IL-1β depended dramatically on the characteristics of the TiO2. Notably, smaller anatase and larger rutile particles provoked higher IL-1β production. In addition, IL-1β production depended on active cathepsin B and reactive oxygen species production independent of the characteristics of TiO2. Our results provide basic information for the creation of safe and effective novel forms of TiO2.