scholarly journals Advanced glycation end products and lipopolysaccharides stimulate interleukin‑6 secretion via the RAGE/TLR4‑NF‑κB‑ROS pathways and resveratrol attenuates these inflammatory responses in mouse macrophages

2017 ◽  
Author(s):  
Ayaka Ohtsu ◽  
Yui Shibutani ◽  
Kotomi Seno ◽  
Hisataka Iwata ◽  
Takehito Kuwayama ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
Mouse Macrophages ◽  
End Products

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 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.

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 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.

Advanced glycation end products elicit externalization of phosphatidylserine in a subpopulation of platelets via 5-HT2A/2Creceptors

2007 ◽  
Vol 293 (1) ◽  
pp. C328-C336 ◽  
Author(s):  
Yingjie Wang ◽  
Werner Beck ◽  
Reinhold Deppisch ◽  
Sally M. Marshall ◽  
Nicholas A. Hoenich ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Inflammatory Responses ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Coagulation Cascade ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products

Advanced glycation end products (AGE) are substantially elevated in individuals with diabetes and/or chronic kidney disease (CKD). These patients are at greatly increased risk of cardiovascular events. The purpose of this study was to investigate the novel hypothesis that AGE elicit externalization of the platelet membrane phospholipid phosphatidylserine (PS). This contributes to hemostasis through propagation of the coagulation cascade leading to thrombus formation. Platelet-rich plasma (PRP) was prepared by differential centrifugation, and PS externalization was quantified by a fluorescence-activated cell sorter using annexin V-FITC. Human serum albumin (HSA)-AGE was generated by incubating HSA with glucose for 2, 4, or 6 wk, and total HSA-AGE was assessed by fluorescence intensity. The 2-wk HSA-AGE preparation (0–2 mg/ml) stimulated a concentration-dependent increase in PS externalization in a subpopulation of platelets that was threefold at 2 mg/ml. In contrast, the 4- and 6-wk preparations were maximal at 0.5 mg/ml and fivefold in magnitude. These effects mirrored the change in total HSA-AGE content of the preparations. The PS response was maximal at 10 min and inhibited by the PKC-δ inhibitor rottlerin and the serotonin [5-hydroxytryptamine (5-HT)]2A/2Creceptor antagonist ritanserin in a dose-dependent manner. Moreover, the 5-HT2A/2Creceptor agonist 1,2,5-dimethoxy-4-iodophenyl-2-aminopropane mimicked the effect of HSA-AGE on PS externalization. These data demonstrate, for the first time, that HSA-AGE stimulates PS externalization in a subpopulation of platelets via the 5-HT2A/2Creceptor. This may have important consequences for platelet involvement in inflammatory responses and the increased cardiovascular risk observed in individuals with diabetes and/or CKD.

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