title: Role of toll-like receptors 3, 4 and 7 in cellular uptake and response to titanium dioxide nanoparticles.
abstract: Innate immune response is believed to be among the earliest provisional cellular responses, and mediates the interactions between microbes and cells. Toll-like receptors (TLRs) are critical to these interactions. We hypothesize that TLRs also play an important role in interactions between nanoparticles (NPs) and cells, although little information has been reported concerning such an interaction. In this study, we investigated the role of TLR3, TLR4 and TLR7 in cellular uptake of titanium dioxide NP (TiO2NP) agglomerates and the resulting inflammatory responses to these NPs. Our data indicate that TLR4 is involved in the uptake of TiO2NPs and promotes the associated inflammatory responses. The data also suggest that TLR3, which has a subcellular location distinct from that of TLR4, inhibits the denaturation of cellular protein caused by TiO2NPs. In contrast, the unique cellular localization of TLR7 has middle-ground functional roles in cellular response after TiO2NP exposure. These findings are important for understanding the molecular interaction mechanisms between NPs and cells.
authors.affiliation: Cell-Materials Interaction Group, Biomaterials Unit, Nano-Bio Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), 1-1, Namiki, Tsukuba, Ibaraki 305-0044, Japan; Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Biotechnology Group, TOTO Ltd Research Institute, Honson 2-8-1, Chigasaki, Kanagawa 253-8577, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Kanehira
authors.affiliation: Cell-Materials Interaction Group, Biomaterials Unit, Nano-Bio Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), 1-1, Namiki, Tsukuba, Ibaraki 305-0044, Japan; Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Taniguchi
keywords: 10.1; first-host defense system; inflammatory response; live cell-based sensor cells; protein denaturation induction; titanium dioxide nanoparticles; toll-like receptor