title: Titanium dioxide induces different levels of IL-1beta production dependent on its particle characteristics through caspase-1 activation mediated by reactive oxygen species and cathepsin B.
abstract: Although titanium dioxide (TiO2) is widely used, its inhalation can induce inflammatory diseases accompanied by interleukin-1beta (IL-1beta) 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-1beta 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-1beta depended dramatically on the characteristics of the TiO2. Notably, smaller anatase and larger rutile particles provoked higher IL-1beta production. In addition, IL-1beta 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.
authors.affiliation: Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morishige
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Aya
authors.initials: A
authors.lastname: Tanabe
authors.forename: Xinglei
authors.initials: X
authors.lastname: Yao
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mukai
authors.forename: Naoki
authors.initials: N
authors.lastname: Okada
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity; D010316:Particle Size; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium; D002401:Cathepsin B; D020170:Caspase 1