PMID- 33466682
OWN - NLM
STAT- MEDLINE
DCOM- 20210909
LR  - 20240330
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 2
DP  - 2021 Jan 14
TI  - Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced 
      Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells.
LID - 10.3390/ijms22020772 [doi]
LID - 772
AB  - Environmental and genetic factors have been demonstrated to contribute to the 
      development of inflammatory bowel disease (IBD). Recent studies suggested that 
      the food additive; titanium dioxide (TiO(2)) might play a causative role in the 
      disease. Therefore, in the present study we aimed to explore the interaction 
      between the food additive TiO(2) and the well-characterized IBD risk gene protein 
      tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the 
      development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced 
      acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid 
      cells (Ptpn2(LysMCre)) or their wild type littermates (Ptpn2(fl/fl)) and exposed 
      to the microparticle TiO(2). The impact of Ptpn2 on TiO(2) signalling pathways 
      and TiO(2)-induced IL-1beta and IL-10 levels were studied using bone marrow-derived 
      macrophages (BMDMs). Ptpn2(LysMCre) exposed to TiO(2) exhibited more severe 
      intestinal inflammation than their wild type counterparts. This effect was likely 
      due to the impact of TiO(2) on the differentiation of intestinal macrophages, 
      suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. 
      Moreover, we also found that TiO(2) was able to induce the secretion of IL-1beta via 
      mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 
      in bone marrow-derived macrophages via MAPK-independent pathways. This is the 
      first evidence of the cooperation between the genetic risk factor Ptpn2 and the 
      environmental factor TiO(2) in the regulation of intestinal inflammation. The 
      results presented here suggest that the ingestion of certain industrial compounds 
      should be taken into account, especially in individuals with increased genetic 
      risk.
FAU - Conde, Javier
AU  - Conde J
AUID- ORCID: 0000-0002-2187-479X
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Schwarzfischer, Marlene
AU  - Schwarzfischer M
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Katkeviciute, Egle
AU  - Katkeviciute E
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Hafliger, Janine
AU  - Hafliger J
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Niechcial, Anna
AU  - Niechcial A
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Brillant, Nathalie
AU  - Brillant N
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Manzini, Roberto
AU  - Manzini R
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Babler, Katharina
AU  - Babler K
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Atrott, Kirstin
AU  - Atrott K
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Lang, Silvia
AU  - Lang S
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
FAU - Scharl, Michael
AU  - Scharl M
AD  - Department of Gastroenterology and Hepatology, University Hospital Zurich, 
      University of Zurich, 8091 Zurich, Switzerland.
LA  - eng
GR  - -/Stiftung fur Experimentelle Biomedizin/
GR  - ECCO Fellowship/European Crohn s and Colitis Organisation/
PT  - Journal Article
DEP - 20210114
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Food Additives)
RN  - 15FIX9V2JP (titanium dioxide)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - D1JT611TNE (Titanium)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 2)
RN  - EC 3.1.3.48 (Ptpn2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Colitis/chemically induced/*genetics/pathology
MH  - Dextran Sulfate
MH  - Female
MH  - Food Additives/*adverse effects
MH  - Gene Deletion
MH  - Genetic Predisposition to Disease
MH  - Inflammatory Bowel Diseases/chemically induced/*genetics/pathology
MH  - Mice
MH  - Myeloid Cells/drug effects/metabolism/*pathology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 2/*genetics
MH  - Titanium/*adverse effects
PMC - PMC7828807
OTO - NOTNLM
OT  - DSS colitis
OT  - macrophages
OT  - titanium dioxide
OT  - ulcerative colitis
COIS- The authors declare no conflict of interest.
EDAT- 2021/01/21 06:00
MHDA- 2021/09/10 06:00
PMCR- 2021/01/14
CRDT- 2021/01/20 01:07
PHST- 2020/11/17 00:00 [received]
PHST- 2021/01/06 00:00 [revised]
PHST- 2021/01/10 00:00 [accepted]
PHST- 2021/01/20 01:07 [entrez]
PHST- 2021/01/21 06:00 [pubmed]
PHST- 2021/09/10 06:00 [medline]
PHST- 2021/01/14 00:00 [pmc-release]
AID - ijms22020772 [pii]
AID - ijms-22-00772 [pii]
AID - 10.3390/ijms22020772 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jan 14;22(2):772. doi: 10.3390/ijms22020772.