From PLoS website: In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
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Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2α. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death.
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Introduction Physical activity levels of children with disabilities are low, as these children and their parents face a wide variety of both personal and environmental barriers. Behavior change techniques support pediatric physical therapists to address these barriers together with parents and children. We developed the What Moves You?! intervention Toolkit (WMY Toolkit) filled with behavioral change tools for use in pediatric physical therapy practice. Objective To evaluate the feasibility of using the WMY Toolkit in daily pediatric physical therapy practice. Methods We conducted a feasibility study with a qualitative approach using semi-structured interviews with pediatric physical therapists (n = 11). After one day of training, the pediatric physical therapists used the WMY Toolkit for a period of 9 weeks, when facilitating physical activity in children with disabilities. We analyzed the transcripts using an inductive thematic analysis followed by a deductive analysis using a feasibility framework. Results For acceptability, pediatric physical therapists found that the toolkit facilitated conversation about physical activity in a creative and playful manner. The working mechanisms identified were in line with the intended working mechanisms during development of the WMY Toolkit, such as focusing on problem solving, self-efficacy and independence. For demand, the pediatric physical therapists mentioned that they were able to use the WMY Toolkit in children with and without disabilities with a broad range of physical activity goals. For implementation, education is important as pediatric physical therapists expressed the need to have sufficient knowledge and to feel confident using the toolkit. For practicality, pediatric physical therapists were positive about the ease of which tools could be adapted for individual children. Some of the design and materials of the toolkit needed attention due to fragility and hygiene. Conclusion The WMY Toolkit is a promising and innovative way to integrate behavior change techniques into pediatric physical therapy practice.
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