Cargando…

Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells

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 th...

Descripción completa

Detalles Bibliográficos
Autores principales: Conde, Javier, Schwarzfischer, Marlene, Katkeviciute, Egle, Häfliger, Janine, Niechcial, Anna, Brillant, Nathalie, Manzini, Roberto, Bäbler, Katharina, Atrott, Kirstin, Lang, Silvia, Scharl, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828807/
https://www.ncbi.nlm.nih.gov/pubmed/33466682
http://dx.doi.org/10.3390/ijms22020772
_version_ 1783641095979139072
author Conde, Javier
Schwarzfischer, Marlene
Katkeviciute, Egle
Häfliger, Janine
Niechcial, Anna
Brillant, Nathalie
Manzini, Roberto
Bäbler, Katharina
Atrott, Kirstin
Lang, Silvia
Scharl, Michael
author_facet Conde, Javier
Schwarzfischer, Marlene
Katkeviciute, Egle
Häfliger, Janine
Niechcial, Anna
Brillant, Nathalie
Manzini, Roberto
Bäbler, Katharina
Atrott, Kirstin
Lang, Silvia
Scharl, Michael
author_sort Conde, Javier
collection PubMed
description 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-1β 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-1β 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
format Online
Article
Text
id pubmed-7828807
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78288072021-01-25 Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells Conde, Javier Schwarzfischer, Marlene Katkeviciute, Egle Häfliger, Janine Niechcial, Anna Brillant, Nathalie Manzini, Roberto Bäbler, Katharina Atrott, Kirstin Lang, Silvia Scharl, Michael Int J Mol Sci Article 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-1β 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-1β 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 MDPI 2021-01-14 /pmc/articles/PMC7828807/ /pubmed/33466682 http://dx.doi.org/10.3390/ijms22020772 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Conde, Javier
Schwarzfischer, Marlene
Katkeviciute, Egle
Häfliger, Janine
Niechcial, Anna
Brillant, Nathalie
Manzini, Roberto
Bäbler, Katharina
Atrott, Kirstin
Lang, Silvia
Scharl, Michael
Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells
title Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells
title_full Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells
title_fullStr Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells
title_full_unstemmed Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells
title_short Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells
title_sort titanium dioxide presents a different profile in dextran sodium sulphate-induced experimental colitis in mice lacking the ibd risk gene ptpn2 in myeloid cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828807/
https://www.ncbi.nlm.nih.gov/pubmed/33466682
http://dx.doi.org/10.3390/ijms22020772
work_keys_str_mv AT condejavier titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT schwarzfischermarlene titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT katkeviciuteegle titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT hafligerjanine titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT niechcialanna titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT brillantnathalie titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT manziniroberto titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT bablerkatharina titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT atrottkirstin titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT langsilvia titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells
AT scharlmichael titaniumdioxidepresentsadifferentprofileindextransodiumsulphateinducedexperimentalcolitisinmicelackingtheibdriskgeneptpn2inmyeloidcells