title: Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome.
abstract: Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO2) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO2in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome.
  
  
  
  Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO2nanoparticles. The proinflammatory effects of TiO2particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO2crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry.
  
  
  
  Oral administration of TiO2nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO2-administered mice. In vitro, TiO2particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1β and IL-18. TiO2also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease.
  
  
  
  These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO2nanoparticles.
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Pedro A
authors: PA
authors: Ruiz
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Belen
authors: B
authors: Morón
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Helen M
authors: HM
authors: Becker
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Silvia
authors: S
authors: Lang
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Kirstin
authors: K
authors: Atrott
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Marianne R
authors: MR
authors: Spalinger
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.|Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors: Michael
authors: M
authors: Scharl
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Kacper A
authors: KA
authors: Wojtal
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Anne
authors: A
authors: Fischbeck-Terhalle
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Isabelle
authors: I
authors: Frey-Wagner
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.
authors: Martin
authors: M
authors: Hausmann
authors: Department of Forensic Pharmacology and Toxicology, Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.
authors: Thomas
authors: T
authors: Kraemer
authors: Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland.|Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors: Gerhard
authors: G
authors: Rogler
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D004396:Coloring Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D014025:Titanium / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood
chemical_list: D004396:Coloring Agents; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D016264:Dextran Sulfate; D014025:Titanium; D020170:Caspase 1
keywords: IMMUNE RESPONSE; INFLAMMATORY BOWEL DISEASE; INFLAMMATORY MECHANISMS; INTESTINAL BARRIER FUNCTION; REACTIVE OXYGEN SPECIES