scholarly journals Dietary Advanced Glycation Endproducts Decrease Glucocorticoid Sensitivity In Vitro

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 441 ◽  
Author(s):  
Timme van der Lugt ◽  
Antje R. Weseler ◽  
Misha F. Vrolijk ◽  
Antoon Opperhuizen ◽  
Aalt Bast
Keyword(s):  
Inflammatory Response ◽  
Glucocorticoid Receptor ◽  
Advanced Glycation Endproducts ◽  
Food Products ◽  
Glucocorticoid Resistance ◽  
Human Macrophage ◽  
Advanced Glycation ◽  
Phosphorylation State ◽  
Glycation Endproducts ◽  
Anti Inflammatory

Glucocorticoids are very effective anti-inflammatory drugs and widely used for inflammatory bowel disease (IBD) patients. However, approximately 20% of IBD patients do not respond to glucocorticoids and the reason for this is largely unknown. Dietary advanced glycation endproducts (AGEs) are formed via the Maillard reaction during the thermal processing of food products and can induce a pro-inflammatory reaction in human cells. To investigate whether this pro-inflammatory response could be mitigated by glucocorticoids, human macrophage-like cells were exposed to both LPS and AGEs to induce interleukin-8 (IL8) secretion. This pro-inflammatory response was then modulated by adding pharmacological compounds interfering in different steps of the anti-inflammatory mechanism of glucocorticoids: rapamycin, quercetin, and theophylline. Additionally, intracellular reactive oxygen species (ROS) were measured and the glucocorticoid receptor phosphorylation state was assessed. The results show that AGEs induced glucocorticoid resistance, which could be mitigated by quercetin and rapamycin. No change in the phosphorylation state of the glucocorticoid receptor was observed. Additionally, intracellular ROS formation was induced by AGEs, which was mitigated by quercetin. This suggests that AGE-induced ROS is an underlying mechanism to AGE-induced glucocorticoid resistance. This study shows for the first time the phenomenon of dietary AGE-induced glucocorticoid resistance due to the formation of ROS. Our findings indicate that food products with a high inflammatory potential can induce glucocorticoid resistance; these results may be of great importance to IBD patients suffering from glucocorticoid resistance.

scholarly journals Dietary Advanced Glycation Endproducts Induce an Inflammatory Response in Human Macrophages in Vitro

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1868 ◽  
Author(s):  
Timme van der Lugt ◽  
Antje Weseler ◽  
Wouter Gebbink ◽  
Misha Vrolijk ◽  
Antoon Opperhuizen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Human Health ◽  
Advanced Glycation Endproducts ◽  
Food Products ◽  
Tnf Alpha ◽  
Human Macrophage ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Rich Food

Advanced glycation endproducts (AGEs) can be found in protein- and sugar-rich food products processed at high temperatures, which make up a vast amount of the Western diet. The effect of AGE-rich food products on human health is not yet clear and controversy still exists due to possible contamination of samples with endotoxin and the use of endogenous formed AGEs. AGEs occur in food products, both as protein-bound and individual molecules. Which form exactly induces a pro-inflammatory effect is also unknown. In this study, we exposed human macrophage-like cells to dietary AGEs, both in a protein matrix and individual AGEs. It was ensured that all samples did not contain endotoxin concentrations > 0.06 EU/mL. The dietary AGEs induced TNF-alpha secretion of human macrophage-like cells. This effect was decreased by the addition of N(ε)-carboxymethyllysine (CML)-antibodies or a receptor for advanced glycation endproducts (RAGE) antagonist. None of the individual AGEs induce any TNF-alpha, indicating that AGEs should be bound to proteins to exert an inflammatory reaction. These findings show that dietary AGEs directly stimulate the inflammatory response of human innate immune cells and help us define the risk of regular consumption of AGE-rich food products on human health.

scholarly journals Gastrointestinal digestion of dietary advanced glycation endproducts using an in vitro model of the gastrointestinal tract (TIM-1)

2020 ◽  
Vol 11 (7) ◽  
pp. 6297-6307 ◽  
Author(s):  
Timme van der Lugt ◽  
Koen Venema ◽  
Stefan van Leeuwen ◽  
Misha F. Vrolijk ◽  
Antoon Opperhuizen ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
In Vitro Model ◽  
Advanced Glycation Endproducts ◽  
Food Products ◽  
Advanced Glycation ◽  
Gastrointestinal Digestion ◽  
Glycation Endproducts ◽  
Vitro Model

In a sophisticated gastrointestinal model, dietary advanced glycation endproducts (dAGEs) in food products remain bound to proteins after digestion and concentrations increase.

scholarly journals The Immune Tolerance Role of the HMGB1-RAGE Axis

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 564
Author(s):  
Haruki Watanabe ◽  
Myoungsun Son
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Lupus Erythematosus ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Chromatin Binding ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Extracellular Milieu

The disruption of the immune tolerance induces autoimmunity such as systemic lupus erythematosus and vasculitis. A chromatin-binding non-histone protein, high mobility group box 1 (HMGB1), is released from the nucleus to the extracellular milieu in particular environments such as autoimmunity, sepsis and hypoxia. Extracellular HMGB1 engages pattern recognition receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation endproducts (RAGE). While the HMGB1-RAGE axis drives inflammation in various diseases, recent studies also focus on the anti-inflammatory effects of HMGB1 and RAGE. This review discusses current perspectives on HMGB1 and RAGE’s roles in controlling inflammation and immune tolerance. We also suggest how RAGE heterodimers responding microenvironments functions in immune responses.

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