Alteration of metabolomic profiles by titanium dioxide nanoparticles in human gingivitis model.
Although nanoparticles (NPs) has afforded considerable benefits in various fields of sciences, several reports have shown their harmful effects, suggesting the necessity of adequate risk assessment. To clarify the mechanism of titanium dioxide nanoparticles (TiO2 NPs)-enhanced gingival inflammation, we conducted the full-scale metabolomic analyses of human gingival fibroblast cells treated with IL-1β alone or in combination with TiO2 NPs. Observation with transmission electron microscope demonstrated the incorporation of TiO2 NPs into vacuoles of the cells. TiO2 NPs significantly enhanced the IL-1β-induced prostaglandin E2 production and COX-1 and COX-2 protein expression. IL-1β reduced the intracellular concentrations of overall primary metabolites especially those of amino acid, urea cycle, polyamine, S-adenosylmethione and glutathione synthetic pathways. The addition of TiO2 NPs further augmented these IL-1β-induced metabolic changes, recommending careful use of dental materials containing TiO2 NPs towards patients with gingivitis or periodontitis. The impact of the present study is to identify the molecular targets of TiO2 NPs for the future establishment of new metabolic markers and therapeutic strategy of gingival inflammation.
Dental and Advanced Studies Research Center (CIEAO), Faculty of Dentistry, Autonomous University State of Mexico, Toluca, Mexico; Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Rene
R
Garcia-Contreras
Institute for Advanced Bioscience, Keio University, Tsuruoka, Yamagata, Japan.
Masahiro
M
Sugimoto
Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Naoki
N
Umemura
Institute for Advanced Bioscience, Keio University, Tsuruoka, Yamagata, Japan.
Miku
M
Kaneko
Institute for Advanced Bioscience, Keio University, Tsuruoka, Yamagata, Japan.
Yoko
Y
Hatakeyama
Institute for Advanced Bioscience, Keio University, Tsuruoka, Yamagata, Japan.
Tomoyoshi
T
Soga
Institute for Advanced Bioscience, Keio University, Tsuruoka, Yamagata, Japan.
Masaru
M
Tomita
Department of Orthodontics, Faculty of Dentistry, Autonomous University State of Mexico, Toluca, Mexico.
Rogelio J
RJ
Scougall-Vilchis
Department of Pediatric Dentistry, Faculty of Dentistry, Autonomous University State of Mexico, Toluca, Mexico.
Rosalia
R
Contreras-Bulnes
Division of Dental Biomaterials Science, Meikai University School of Dentistry, Sakado, Saitama, 350-0283, Japan.
Hiroshi
H
Nakajima
Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan. Electronic address: sakagami@dent.meikai.ac.jp.
Hiroshi
H
Sakagami
D002478:Cells, Cultured; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005881:Gingiva / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005891:Gingivitis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D055442:Metabolome; D053758:Nanoparticles / Q000009:adverse effects*; D015398:Signal Transduction; D014025:Titanium / Q000009:adverse effects*
D053583:Interleukin-1beta; C009495:titanium dioxide; D014025:Titanium
Human gingival fibroblast; Inerleukin-1β; Inflammation; Metabolomics; Titanium dioxide nanoparticle