title: Inhalation of titanium dioxide induces endoplasmic reticulum stress-mediated autophagy and inflammation in mice.
abstract: Titanium dioxide (TiO2) nanoparticles are widely used in cosmetics, sunscreen, electronics, drug delivery systems, and diverse bio-application fields. In the workplace, the primary exposure route for TiO2 nanoparticles is inhalation through the respiratory system. Because TiO2 nanoparticles have different physiological properties, in terms of size and bioactivity, their toxic effects in the respiratory system must be determined. In this study, to determine the toxic effect of inhaled TiO2 nanoparticles in the lung and the underlying mechanism, we used a whole-body chamber inhalation system to expose A/J mice to TiO2 nanoparticles for 28 days. During the experiments, the inhaled TiO2 nanoparticles were characterized using a cascade impactor and transmission electron microscopy. After inhalation of the TiO2 nanoparticles, hyperplasia and inflammation were observed in a TiO2 dose-dependent manner. To determine the biological mechanism of the toxic response in the lung, we examined endoplasmic reticulum (ER) and mitochondria in lung. The ER and mitochondria were disrupted and dysfunctional in the TiO2-exposed lung leading to abnormal autophagy. In summary, we assessed the potential risk of TiO2 nanoparticles in the respiratory system, which contributed to our understanding of the mechanism underlining TiO2 nanoparticle toxicity in the lung.
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Kyeong-Nam
authors.initials: KN
authors.lastname: Yu
authors.affiliation: Toxicity Evaluation Center, Korea Conformity Laboratories, Incheon, South Korea.
authors.forename: Jae Hyuck
authors.initials: JH
authors.lastname: Sung
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, South Korea; Toxicity Evaluation Center, Korea Conformity Laboratories, Incheon, South Korea.
authors.forename: Somin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, South Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul, South Korea.
authors.forename: Sanghwa
authors.initials: S
authors.lastname: Kim
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, South Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul, South Korea.
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Cho
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Lee
authors.affiliation: R&D Center, Biterials, Goyang, South Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Lim
authors.affiliation: Department of Pathology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Changhoon
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Pathology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Chanhee
authors.initials: C
authors.lastname: Chae
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Toxicity Evaluation Center, Korea Conformity Laboratories, Incheon, South Korea.
authors.forename: Jinkyu
authors.initials: J
authors.lastname: Lee
authors.affiliation: R&D Center, Biterials, Goyang, South Korea. Electronic address: lifeisgood@biterials.com.
authors.forename: Jun-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, South Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul, South Korea; Graduate School of Convergence Science and Technology, Seoul National University, Suwon, South Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon, South Korea; Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, South Korea. Electronic address: mchotox@snu.ac.kr.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000818:Animals; D001273:Atmosphere Exposure Chambers; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D006965:Hyperplasia; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D008805:Mice, Inbred A; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D010316:Particle Size; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D012720:Severity of Illness Index; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*; D059551:Toxicity Tests, Subacute
chemical_list: D015415:Biomarkers; C009495:titanium dioxide; D014025:Titanium
keywords: Autophagy; ER stress; Inflammation; Inhalation; Lung; Titanium dioxide (TiO(2)) nanoparticle