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Comparison of Cellular Uptake and Inflammatory Response via Toll-Like Receptor 4 to Lipopolysaccharide and Titanium Dioxide Nanoparticles
Cell-Materials Interaction Group, Biomaterials Unit, Nano-Life Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 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
Biotechnology Group, TOTO Ltd. Research Institute, Honson 2-8-1, Chigasaki, Kanagawa 253-8577, Japan
* Author to whom correspondence should be addressed.
Received: 9 May 2013; in revised form: 10 June 2013 / Accepted: 17 June 2013 / Published: 26 June 2013
Abstract: The innate immune response is the earliest cellular response to infectious agents and mediates the interactions between microbes and cells. Toll-like receptors (TLRs) play an important role in these interactions. We have already shown that TLRs are involved with the uptake of titanium dioxide nanoparticles (TiO2 NPs) and promote inflammatory responses. In this paper, we compared role of cellular uptake and inflammatory response via TLR 4 to lipopolysaccharide (LPS) and TiO2 NPs. In the case of LPS, LPS binds to LPS binding protein (LBP) and CD 14, and then this complex binds to TLR 4. In the case of TiO2 NPs, the necessity of LBP and CD 14 to induce the inflammatory response and for uptake by cells was investigated using over-expression, antibody blocking, and siRNA knockdown experiments. Our results suggested that for cellular uptake of TiO2 NPs, TLR 4 did not form a complex with LBP and CD 14. In the TiO2 NP-mediated inflammatory response, TLR 4 acted as the signaling receptor without protein complex of LPS, LBP and CD 14. The results suggested that character of TiO2 NPs might be similar to the complex of LPS, LBP and CD 14. These results are important for development of safer nanomaterials.
Keywords: toll-like receptors; titanium dioxide nanoparticles; LPS binding protein; CD 14
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MDPI and ACS Style
Mano, S.S.; Kanehira, K.; Taniguchi, A. Comparison of Cellular Uptake and Inflammatory Response via Toll-Like Receptor 4 to Lipopolysaccharide and Titanium Dioxide Nanoparticles. Int. J. Mol. Sci. 2013, 14, 13154-13170.
Mano SS, Kanehira K, Taniguchi A. Comparison of Cellular Uptake and Inflammatory Response via Toll-Like Receptor 4 to Lipopolysaccharide and Titanium Dioxide Nanoparticles. International Journal of Molecular Sciences. 2013; 14(7):13154-13170.
Mano, Sharmy S.; Kanehira, Koki; Taniguchi, Akiyoshi. 2013. "Comparison of Cellular Uptake and Inflammatory Response via Toll-Like Receptor 4 to Lipopolysaccharide and Titanium Dioxide Nanoparticles." Int. J. Mol. Sci. 14, no. 7: 13154-13170.