Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy

As of late, evidence has been emerging that the Maillard reaction (MR, also referred to as glycation) affects the structure and function of food proteins. MR induces the conformational and chemical modification of food proteins, not only on the level of IgG/IgE recognition, but also by increasing the interaction and recognition of these modified proteins by antigen-presenting cells (APCs). This affects their biological properties, including digestibility, bioavailability, immunogenicity, and ultimately their allergenicity. APCs possess various receptors that recognize glycation structures, which include receptor for advanced glycation end products (RAGE), scavenger receptors (SRs), galectin-3 and CD36. Through these receptors, glycation structures may influence the recognition, uptake and antigen-processing of food allergens by dendritic cells (DCs) and monocytes. This may lead to enhanced cytokine production and maturation of DCs, and may also induce adaptive immune responses to the antigens/allergens as a result of antigen uptake, processing and presentation to T cells. Here, we aim to review the current literature on the immunogenicity of AGEs originating from food (exogenous or dietary AGEs) in relation to AGEs that are formed within the body (endogenous AGEs), their interactions with receptors present on immune cells, and their effects on the activation of the innate as well as the adaptive immune system. Finally, we review the clinical relevance of AGEs in food allergies.

Download Full-text

Advanced Glycation End Products (AGEs) May Be a Striking Link Between Modern Diet and Health

Biomolecules ◽

10.3390/biom9120888 ◽

2019 ◽

Vol 9 (12) ◽

pp. 888 ◽

Cited By ~ 12

Author(s):

Vidhu Gill ◽

Vijay Kumar ◽

Kritanjali Singh ◽

Ashok Kumar ◽

Jong-Joo Kim

Keyword(s):

High Temperature ◽

Advanced Glycation End Products ◽

The Body ◽

Food Allergies ◽

Post Translational Modification ◽

Advanced Glycation ◽

Formula Milk ◽

Uremic Cardiomyopathy ◽

Glycation End Products ◽

End Products

The Maillard reaction is a simple but ubiquitous reaction that occurs both in vivo and ex vivo during the cooking or processing of foods under high-temperature conditions, such as baking, frying, or grilling. Glycation of proteins is a post-translational modification that forms temporary adducts, which, on further crosslinking and rearrangement, form permanent residues known as advanced glycation end products (AGEs). Cooking at high temperature results in various food products having high levels of AGEs. This review underlines the basis of AGE formation and their corresponding deleterious effects on the body. Glycated Maillard products have a direct association with the pathophysiology of some metabolic diseases, such as diabetes mellitus type 2 (DM2), acute renal failure (ARF), Alzheimer’s disease, dental health, allergies, and polycystic ovary syndrome (PCOS). The most glycated and structurally abundant protein is collagen, which acts as a marker for diabetes and aging, where decreased levels indicate reduced skin elasticity. In diabetes, high levels of AGEs are associated with carotid thickening, ischemic heart disease, uremic cardiomyopathy, and kidney failure. AGEs also mimic hormones or regulate/modify their receptor mechanisms at the DNA level. In women, a high AGE diet directly correlates with high levels of androgens, anti-Müllerian hormone, insulin, and androstenedione, promoting ovarian dysfunction and/or infertility. Vitamin D3 is well-associated with the pathogenesis of PCOS and modulates steroidogenesis. It also exhibits a protective mechanism against the harmful effects of AGEs. This review elucidates and summarizes the processing of infant formula milk and the associated health hazards. Formulated according to the nutritional requirements of the newborn as a substitute for mother’s milk, formula milk is a rich source of primary adducts, such as carboxy-methyl lysine, which render an infant prone to inflammation, dementia, food allergies, and other diseases. We therefore recommend that understanding this post-translational modification is the key to unlocking the mechanisms and physiology of various metabolic syndromes.

Download Full-text

Yiqi Huoxue Recipe Regulates Autophagy through Degradation of Advanced Glycation End Products via mTOR/S6K1/LC3 Pathway in Diabetic Nephropathy

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9942678 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Liang Chen ◽

Linghao Dai ◽

Yi Liu ◽

Xinyue Li ◽

Hui Wang

Keyword(s):

Body Weight ◽

Diabetic Nephropathy ◽

Advanced Glycation End Products ◽

Periodic Acid ◽

The Body ◽

Advanced Glycation ◽

Kidney Weight ◽

Expression Levels ◽

Glycation End Products ◽

End Products

Background. Yiqi Huoxue recipe can delay the progression of diabetic nephropathy, but its treatment mechanism is still unclear. We aimed to explore the effects of Yiqi Huoxue recipe on autophagy in diabetic nephropathy and its underlying mechanism. Methods. All rats were randomly divided into seven groups. The body weight, kidney weight, blood glucose, glycated hemoglobin, urine protein, urine microprotein, creatinine, urea nitrogen, triglyceride, and lipoprotein were analyzed. HE, Masson, and periodic acid-Schiff staining were used to detect the severity of pathological changes in kidneys. The level of advanced glycation end products was assessed by the ELISA. Immunofluorescence staining was performed to check the expressions of podocin and nephrin. The expression levels of mTOR/S6K1/LC3 pathway-related proteins and mRNA were detected by qRT-PCR and western blotting. Results. Yiqi Huoxue recipe significantly elevated body weight and significantly decreased kidney weight and kidney index. Yiqi Huoxue recipe significantly affected the levels of biochemical indicators in diabetic nephropathy and showed a regulatory effect on kidney damage and lipid metabolism disorders. ELISA showed that Yiqi Huoxue recipe significantly reduced the level of advanced glycation end products. The expressions of nephrin and podocin increased significantly, depending on the dosage of Yiqi Huoxue recipe. Additionally, Yiqi Huoxue recipe regulated the expression levels of p-AKT, mTOR, S6K1, and LC3. Conclusion. Yiqi Huoxue recipe regulates podocyte autophagy to promote the degradation of advanced glycation end products through mTOR/S6K1/LC3 pathway. It has a certain guiding significance for the diagnosis and treatment of diabetic nephropathy.

Download Full-text

Role of Advanced Glycation End Products in Carcinogenesis and their Therapeutic Implications

Current Pharmaceutical Design ◽

10.2174/1381612825666190130145549 ◽

2019 ◽

Vol 24 (44) ◽

pp. 5245-5251 ◽

Cited By ~ 11

Author(s):

David Schröter ◽

Annika Höhn

Keyword(s):

Advanced Glycation End Products ◽

Molecular Mechanisms ◽

The Body ◽

Advanced Glycation ◽

Therapeutic Implications ◽

Age Related ◽

Glycation End Products ◽

End Products ◽

Reduction Strategies

Aging is one of the biggest risk factors for the major prevalent diseases such as cardiovascular diseases, neurodegeneration and cancer, but due to the complex and multifactorial nature of the aging process, the molecular mechanisms underlying age-related diseases are not yet fully understood. Research has been intensive in the last years aiming to characterize the pathophysiology of aging and develop therapies to fight age-related diseases. In this context advanced glycation end products (AGEs) have received attention. AGEs, when accumulated in tissues, significantly increase the level of inflammation in the body which has long been associated with the development of cancer. Here we discuss the classical settings promoting AGE formation, as well as reduction strategies, occurrence and relevance of AGEs in cancer tissues and the role of AGE-interaction with the receptor for advanced glycation end products (RAGE) in cancer initiation and progression.

Download Full-text

Resveratrol Prevents Dendritic Cell Maturation in Response to Advanced Glycation End Products

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/574029 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 18

Author(s):

Brigitta Buttari ◽

Elisabetta Profumo ◽

Francesco Facchiano ◽

Elif Inci Ozturk ◽

Luca Segoni ◽

...

Keyword(s):

Dendritic Cell ◽

Advanced Glycation End Products ◽

Map Kinases ◽

Human Monocyte ◽

Inhibitory Effect ◽

The Body ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products

Advanced glycation end products (AGEs), generated through nonenzymatic glycosylation of proteins, lipids, and nucleic acids, accumulate in the body by age thus being considered as biomarkers of senescence. Senescence is characterized by a breakdown of immunological self-tolerance, resulting in increased reactivity to self-antigens. Previous findings suggest that AGE and its receptor RAGE may be involved in the pathogenesis of autoimmune reactions through dendritic cell (DC) activation. The aim of this study was to investigate whether resveratrol, a polyphenolic antioxidant compound with tolerogenic effects on DCs, was able to counteract the mechanisms triggered by AGE/RAGE interaction on DCs. By immunochemical and cytofluorimetric assays, we demonstrated thatin vitropretreatment of human monocyte-derived DCs with resveratrol prevents DC activation in response to glucose-treated albumin (AGE-albumin). We found that resveratrol exerts an inhibitory effect on DC surface maturation marker and RAGE up-regulation in response to AGE-albumin. It also inhibited proinflammatory cytokine expression, allostimulatory ability upregulation, mitogen-activated protein (MAP) kinases, and NF-κB activation in AGE-albumin-stimulated DCs. We suggest that resveratrol, by dismantling AGE/RAGE signaling on DCs may prevent or reduce increased reactivity to self-molecules in aging.

Download Full-text

Advanced Glycation End-Products Can Activate or Block Bitter Taste Receptors

Nutrients ◽

10.3390/nu11061317 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1317 ◽

Cited By ~ 2

Author(s):

Appalaraju Jaggupilli ◽

Ryan Howard ◽

Rotimi E. Aluko ◽

Prashen Chelikani

Keyword(s):

Advanced Glycation End Products ◽

Bitter Taste ◽

The Body ◽

Taste Perception ◽

Taste Receptors ◽

Binding Affinities ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Bitter Taste Receptors

Bitter taste receptors (T2Rs) are expressed in several tissues of the body and are involved in a variety of roles apart from bitter taste perception. Advanced glycation end-products (AGEs) are produced by glycation of amino acids in proteins. There are varying sources of AGEs, including dietary food products, as well as endogenous reactions within our body. Whether these AGEs are T2R ligands remains to be characterized. In this study, we selected two AGEs, namely, glyoxal-derived lysine dimer (GOLD) and carboxymethyllysine (CML), based on their predicted interaction with the well-studied T2R4, and its physiochemical properties. Results showed predicted binding affinities (Kd) for GOLD and CML towards T2R4 in the nM and μM range, respectively. Calcium mobilization assays showed that GOLD inhibited quinine activation of T2R4 with IC50 10.52 ± 4.7 μM, whilst CML was less effective with IC50 32.62 ± 9.5 μM. To characterize whether this antagonism was specific to quinine activated T2R4 or applicable to other T2Rs, we selected T2R14 and T2R20, which are expressed at significant levels in different human tissues. A similar effect of GOLD was observed with T2R14; and in contrast, GOLD and CML activated T2R20 with an EC50 of 79.35 ± 29.16 μM and 65.31 ± 17.79 μM, respectively. In this study, we identified AGEs as novel T2R ligands that caused either activation or inhibition of different T2Rs.

Download Full-text

Advanced glycation end products and their receptors in serum of patients with type 2 diabetes

Scientific Reports ◽

10.1038/s41598-021-92630-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Diana Indyk ◽

Agnieszka Bronowicka-Szydełko ◽

Andrzej Gamian ◽

Aleksandra Kuzan

Keyword(s):

Type 2 Diabetes ◽

Advanced Glycation End Products ◽

Hdl Cholesterol ◽

The Body ◽

Advanced Glycation ◽

Serum Samples ◽

Patients Âgés ◽

Glycation End Products ◽

End Products

AbstractGlycation is a non-enzymatic process involving the reaction of reducing sugars or reactive oxoaldehyde with proteins, lipids or nucleic acids, which results in the formation of advanced glycation end products (AGEs). The presented work discusses the glycation process in people with advanced stage of type 1 or type 2 diabetes. The concentration of different AGEs and their receptors for 58 serum samples was determined by ELISA and by spectrofluorimetric methods. In addition to fluorescent low molecular weight and protein-bound AGEs, we have also marked a new class of AGEs: melibiose-derived glycation product (MAGE). Our attention was also focused on the two groups of AGEs receptors: scavenger receptors (SR-A and SR-B) and RAGE. The correlation between the SR-AI scavenging receptors concentration and the fluorescence of AGEs as well as diabetes biological markers: GFR, creatinine contentration and HbA1c was demonstrated. A relationship between the concentration of AGEs and their receptors was also found in serum sample of patients treated with the metformin and aspirin. Furthermore, the concentration of SR-AI scavenger and the fluorescence of total AGEs was significantly lower in treated patients than in non treated patients. AGEs have also been found to contribute to the development of cardiovascular disease, atherosclerosis and diabetic complications, what could be deduced from the correlation of AGEs level and HDL cholesterol or uric acid level. Thus, it was confirmed that AGEs are involved in the pathomechanism of diabetes and other degenerative diseases. Nowadays, it is believed that AGEs due to the long time remaining in the body may be an important diagnostic marker. Their determination may allow monitoring the progression of the disease and the effectiveness of the therapy.

Download Full-text