scholarly journals Relevance of Receptor for Advanced Glycation end Products (RAGE) in Murine Antibody-Mediated Autoimmune Diseases

2019 ◽  
Vol 20 (13) ◽  
pp. 3234
Author(s):  
Alexandra Eichhorst ◽  
Christoph Daniel ◽  
Rita Rzepka ◽  
Bettina Sehnert ◽  
Falk Nimmerjahn ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Diseases ◽  
Advanced Glycation End Products ◽  
Plasma Cells ◽  
Inflammatory Responses ◽  
Joint Inflammation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

It is incompletely understood how self-antigens become targets of humoral immunity in antibody-mediated autoimmune diseases. In this context, alarmins are discussed as an important level of regulation. Alarmins are recognized by various receptors, such as receptor for advanced glycation end products (RAGE). As RAGE is upregulated under inflammatory conditions, strongly binds nucleic acids and mediates pro-inflammatory responses upon alarmin recognition, our aim was to examine its contribution to immune complex-mediated autoimmune diseases. This question was addressed employing RAGE−/− animals in murine models of pristane-induced lupus, collagen-induced, and serum-transfer arthritis. Autoantibodies were assessed by enzyme-linked immunosorbent assay, renal disease by quantification of proteinuria and histology, arthritis by scoring joint inflammation. The associated immune status was determined by flow cytometry. In both disease entities, we detected tendentiously decreased autoantibody levels in RAGE−/− mice, however no differences in clinical outcome. In accordance with autoantibody levels, a subgroup of the RAGE−/− animals showed a decrease in plasma cells, and germinal center B cells and an increase in follicular B cells. Based on our results, we suggest that RAGE deficiency alone does not significantly affect antibody-mediated autoimmunity. RAGE may rather exert its effects along with other receptors linking environmental factors to auto-reactive immune responses.

scholarly journals Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes: a comparative cross-sectional study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Eva O. Melin ◽  
Jonatan Dereke ◽  
Magnus Hillman
Keyword(s):  
Type 1 Diabetes ◽  
Advanced Glycation End Products ◽  
Inflammatory Responses ◽  
Lipid Lowering ◽  
Advanced Glycation ◽  
Cross Sectional ◽  
Lipid Lowering Drugs ◽  
Glycation End Products ◽  
End Products

Abstract Background The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D). Methods Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed. Results In this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P <  0.001), and triglycerides (P <  0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values < 0.043), were associated with AHD. Conclusions Higher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.

scholarly journals Endogenous Secretory Receptor for Advanced Glycation End Products Protects Endothelial Cells from AGEs Induced Apoptosis

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Guomin Yang ◽  
Yinqiong Huang ◽  
Xiaohong Wu ◽  
Xiahong Lin ◽  
Jinting Xu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Advanced Glycation End Products ◽  
Proinflammatory Cytokine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Glycation End Products ◽  
End Products

Endogenous secretory receptor for advanced glycation end products (esRAGE) binds extracellular RAGE ligands and blocks RAGE activation on the cell surface, protecting endothelial cell function. However, the underlying mechanism remains unclear. Endothelial cells overexpressing the esRAGE gene were generated using a lentiviral vector. Then, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to assess esRAGE mRNA and protein levels, respectively. Hoechst-PI double staining was used to assess apoptosis. Western blot and qRT-PCR were used to assess the expression levels of apoptosis-related factors and the proinflammatory cytokine NF-кB. Compared with the control group, AGEs significantly induced endothelial cell apoptosis, which was significantly reduced by esRAGE overexpression. Incubation with AGEs upregulated the proapoptotic factor Bax and downregulated the antiapoptotic factor Bcl-2. Overexpression of esRAGE reduced Bax expression induced by AGEs and increased Bcl-2 levels. Furthermore, AGEs increased the expression levels of proinflammatory cytokine NF-кB, which were reduced after esRAGE overexpression. esRAGE protects endothelial cells from AGEs associated apoptosis, by downregulating proapoptotic (Bax) and inflammatory (NF-кB) factors and upregulating the antiapoptotic factor Bcl-2.

Rehmannia glutinosa Suppresses Inflammatory Responses Elicited by Advanced Glycation End Products

Inflammation ◽  
2012 ◽  
Vol 35 (4) ◽  
pp. 1232-1241 ◽  
Author(s):  
Gui-Hyun Baek ◽  
Yong-Suk Jang ◽  
Seung-Il Jeong ◽  
Jaeho Cha ◽  
Myungsoo Joo ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Inflammatory Responses ◽  
Rehmannia Glutinosa ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals Elevated level of the soluble receptor for advanced glycation end-products involved in sarcopenia: an observational study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shou-En Wu ◽  
Yi-Lin Chiu ◽  
Tung-Wei Kao ◽  
Wei-Liang Chen
Keyword(s):  
Muscle Mass ◽  
Advanced Glycation End Products ◽  
Community Dwelling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Health Examination ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Srage Level ◽  
Glycation End Products ◽  
End Products

Abstract Background The soluble receptor for advanced glycation end products (sRAGE) has been proposed to serve as a marker for disease severity, but its role in sarcopenia, an age-related progressive loss of muscle mass and function, remains elusive. This study examines the association between sRAGE and sarcopenia. Methods A total of 314 community-dwelling elderly adults who had their health examination at Tri-Service General Hospital from 2017 to 2019 underwent protein analysis with enzyme-linked immunosorbent assay. The relationship with sarcopenia and its detailed information, including components and diagnosis status, were examined using linear and logistic regressions. Results As for sarcopenia components, low muscle mass (β = 162.8, p = 0.012) and strength (β = 181.31, p = 0.011) were significantly correlated with sRAGE, but not low gait speed (p = 0.066). With regard to disease status, confirmed sarcopenia (β = 436.93, p < 0.001), but not probable (p = 0.448) or severe sarcopenia (p = 0.488), was significantly correlated with sRAGE. In addition, females revealed a stronger association with sRAGE level by showing significant correlations with low muscle mass (β = 221.72, p = 0.014) and low muscle strength (β = 208.68, p = 0.043). Conclusions sRAGE level showed a positive association with sarcopenia, illustrating its involvement in the evolution of sarcopenia. This association is more evident in female groups, which may be attributed to the loss of protection from estrogen in postmenopausal women. Utilizing sRAGE level as a prospective marker for sarcopenia deserves further investigation in future studies.

scholarly journals Circulating soluble receptor for advanced glycation end products and other factors in type 2 diabetes patients with colorectal cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaohai Zhou ◽  
Ning Lin ◽  
Mingjie Zhang ◽  
Xiaoling Wang ◽  
Ye An ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Total Cholesterol ◽  
Advanced Glycation End Products ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Diabetes Patients

Abstract Background Recent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients. Methods A total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization. Results Type 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037–5.051; P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377, P < 0.001), total cholesterol (r = 0.491, P < 0.001), and low-density lipoprotein cholesterol (LDL-c)(r = 0.330, P < 0.001) levels; the homeostatic model assessment for insulin resistance(HOMA-IR)score (r = 0.194, P = 0.017); and fasting serum insulin (r = 0.167, P = 0.041) and IL-6 (r = 0.311, P < 0.001) concentrations. Conclusions Our results suggested that circulating sRAGE is independently risk factor for CRC, and also closely related to inflammation, dyslipidemia in type 2 diabetes patients.

scholarly journals Plasma Catestatin Levels and Advanced Glycation End Products in Patients on Hemodialysis

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 456
Author(s):  
Mirko Luketin ◽  
Maja Mizdrak ◽  
Dijana Boric-Skaro ◽  
Dinko Martinovic ◽  
Daria Tokic ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Advanced Glycation End Products ◽  
Significant Positive Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Advanced Glycation ◽  
Positive Correlation ◽  
Glycation End Products ◽  
End Products ◽  
Stage Renal Disease

Catestatin (CST) is a pleiotropic peptide involved in cardiovascular protection with its antihypertensive and angiogenic effects. Considering that patients with end-stage renal disease (ESRD) who are undergoing hemodialysis (HD) are associated with higher cardiovascular risk, the aim of this study was to investigate plasma CST levels in HD patients, compare them to healthy controls and evaluate possible CST associations with advanced glycation end products (AGEs) and laboratory, anthropometric and clinical parameters. The study included 91 patients on HD and 70 healthy controls. Plasma CST levels were determined by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit, while AGEs were determined using skin autofluorescence. Plasma CST levels were significantly higher in the HD group compared to the controls (32.85 ± 20.18 vs. 5.39 ± 1.24 ng/mL, p < 0.001) and there was a significant positive correlation between CST and AGEs (r = 0.492, p < 0.001). Furthermore, there was a significant positive correlation between plasma CST levels with both the Dialysis Malnutrition Score (r = 0.295, p = 0.004) and Malnutrition-Inflammation Score (r = 0.290, p = 0.005). These results suggest that CST could be playing a role in the complex pathophysiology of ESRD/HD and that it could affect the higher cardiovascular risk of patients on HD.

scholarly journals 6-Shogaol Inhibits Advanced Glycation End-Products-Induced IL-6 and ICAM-1 Expression by Regulating Oxidative Responses in Human Gingival Fibroblasts

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3705 ◽  
Author(s):  
Nonaka ◽  
Bando ◽  
Sakamoto ◽  
Inagaki ◽  
Naruishi ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Heme Oxygenase 1 ◽  
Gingival Fibroblasts ◽  
Advanced Glycation ◽  
Periodontal Tissues ◽  
Glycation End Products ◽  
End Products ◽  
Oxidative Responses

Advanced glycation end-products (AGEs) cause diabetes mellitus (DM) complications and accumulate more highly in periodontal tissues of patients with periodontitis and DM. AGEs aggravate periodontitis with DM by increasing the expression of inflammation-related factors in periodontal tissues. 6-Shogaol, a major compound in ginger, has anti-inflammatory and anti-oxidative activities. However, the influence of shogaol on DM-associated periodontitis is not well known. In this study, the effects of 6-shogaol on AGEs-induced oxidative and anti-oxidative responses, and IL-6 and ICAM-1 expression in human gingival fibroblasts (HGFs) were investigated. When HGFs were cultured with 6-shogaol and AGEs, the activities of reactive oxygen species (ROS) and antioxidant enzymes (heme oxygenase-1 [HO-1] and NAD(P)H quinone dehydrogenase 1 [NQO1]), and IL-6 and ICAM-1 expressions were investigated. RAGE expression and phosphorylation of MAPKs and NF-κB were examined by western blotting. 6-Shogaol significantly inhibited AGEs-induced ROS activity, and increased HO-1 and NQO1 levels compared with the AGEs-treated cells. The AGEs-stimulated expression levels of receptor of AGE (RAGE), IL-6 and ICAM-1 and the phosphorylation of p38, ERK and p65 were attenuated by 6-shogaol. These results suggested that 6-shogaol inhibits AGEs-induced inflammatory responses by regulating oxidative and anti-oxidative activities and may have protective effects on periodontitis with DM.

JPMA-2020-01-184 Association analysis of -429T/C receptor for advanced glycation end products (RAGE) gene polymorphism with type 2 diabetic retinopathy and serum soluble RAGE levels in Pakistani patients

2020 ◽  
pp. 1-16
Author(s):  
Shazia Qayyum ◽  
Muhammad Afzal ◽  
Abdul Khaliq Naveed ◽  
Admin
Keyword(s):  
Diabetic Retinopathy ◽  
Gene Polymorphism ◽  
Advanced Glycation End Products ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Allelic Frequencies ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Abstract Objective: To investigate the association of receptor for advanced glycation end products (RAGE) gene polymorphism 429T/C (rs1800625) with diabetic retinopathy (DR) and serum soluble RAGE (sRAGE) levels in Pakistani patients with Type 2 diabetes. Methods: A case-control study, conducted from January 2017 to December 2018, including 150 healthy controls (HC), 150 diabetics without retinopathy (DWR) and 150 DR patients. Ethical approval was taken from Ethics Review Committee of Islamic International Medical College - Riphah International University (RIU). Genotyping for 429T/C was done by Tetra-primer amplification refractory mutation system – polymerase chain reaction (T-ARMS-PCR). Serum sRAGE levels were measured by enzyme-linked immunosorbent assay (ELISA). Data was analysed to calculate descriptive and inferential statistics to compare genotype/allelic frequencies, biochemical markers and serum sRAGE among three study groups. Results: The frequency of TT, TC and CC genotypes of 429T/C polymorphism were: 91.3%, 6.7%, 2% in HC, 88.6%, 8.7%, 2.7% in DWR and 84.7%, 12.0%, 3.3 % in DR groups. No significant association of 429T/C genotypic and allelic frequencies with DWR and DR along with its subtypes, non- proliferative (NPDR) and proliferative (PDR) was observed. Upon further stratifying NPDR into mild, moderate and severe, an association of heterozygous TC with severe NPDR was observed compared to DWR in univariate and multinomial regression analysis. Serum sRAGE levels were significantly high in PDR patients compared to DWR and were positively correlated with fasting plasma glucose (FPG) in DR group.  

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