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

Abstract

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 (TiO2) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO2 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 (Ptpn2LysMCre) or their wild type littermates (Ptpn2fl/fl) and exposed to the microparticle TiO2. The impact of Ptpn2 on TiO2 signalling pathways and TiO2-induced IL-1β and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2LysMCre exposed to TiO2 exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO2 on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO2 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 TiO2 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

Hydroxyapatite-coated titanium oxide ameliorates dextran sulphate sodium-induced colitis by attenuating both innate and acquired immune reaction

“…Our results are in contrast to previous results for TiO 2 nanoparticles that exacerbated DSS-induced coli- tis [11][12][13]. The different results may indicate a fundamental difference in the relationship between the TiO 2 nanoparticles and HA-coated TiO 2 .…”

Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn’s disease in Indian

“…More than 240 genetic susceptibility loci have been identified for IBD[ 15 ]. Many of them are also associated with risk of other diseases.…”

Inflammation in Health and Disease: New Insights and Therapeutic Avenues

“…The latter is not only relevant for their interference with the normal function of the endocrine system, but endocrine disruptors can also participate in the pathophysiology of non-alcoholic fatty liver disease (NAFLD) (as reviewed by Cano et al) by modulating liver metabolism [ 22 ]. In the same way, the food additive titanium dioxide worsened experimental colitis in mice carrying IBD genetic risk mutations [ 23 ], suggesting that the ingestion of industrial compounds can be detrimental to patients with IBD with an increased genetic predisposition. Silicon dioxide is well-known for causing lung silicosis, and novel pathophysiological mechanisms and treatment options were reviewed by Adamcakova et al [ 24 ].…”