AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An Alternative Inflammatory Mechanism?

Serban, Andreea Iren; Stanca, Loredana; Geicu, Ovidiu Ionuț; Dinischiotu, Anca

doi:10.3390/ijms160920100

Cited by 21 publications

(20 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This difference between the two inflammatory pathways was evident during the 6-12 hour period of treatment (T1) with sRAGE being lower in comparison to the rapid increase in the majority of cytokines, possibly initiated by insulin treatment (4,5,8,9). While interactions between components of the two pathways are likely (37,38,39), we were unable to confirm interactions in this study. Of interest, we also noted a difference in sRAGE concentrations at three months post-DKA therapy by ethnicity and gender with C having significantly higher (p=0.003) sRAGE concentrations compared with AA and this concentration was also significantly higher (p=0.04) in females than males.…”

Section: Discussionmentioning

confidence: 63%

Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis

Hoffman

Ishikawa

Blum

et al. 2020

Jcrpe

View full text Add to dashboard Cite

To determine the time relationships of soluble receptor for glycation end-products (sRAGE), [a decoy of the advanced glycation end-products (AGE)-RAGE axis] and D-lactate, (a metabolite of methylglyoxal) in the inflammatory response to diabetic ketoacidosis (DKA). Methods: Sixteen children and adolescents with type 1 diabetes (T1D) had blood samples obtained, 6-12 hours into treatment, at three weeks and three months post start of treatment. sRAGE and D-lactate concentrations at three months were considered baseline. Expression of RAGE was investigated in the myocardium of a newly diagnosed and untreated young person with fatal T1D/DKA. Results: sRAGE 6-12 hours after the start of treatment was 39% lower than the values at two weeks (p=0.0036) and at three months (p=0.0023) post treatment. D-lactate was higher during treatment than at three weeks (p=0.04) and at three months (p=0.035). Conclusion: sRAGE concentration was decreased during treatment, compared to concentrations at two weeks and three months after treatment. The increased D-lactate during treatment was in keeping with the known increase in dicarbonyls at this time. The finding of RAGE expression in a young myocardium prior to DKA treatment suggested cardiovascular inflammation pre-treatment and at a young age.

show abstract

Section: Discussionmentioning

confidence: 63%

Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis

Hoffman

Ishikawa

Blum

et al. 2020

Jcrpe

View full text Add to dashboard Cite

show abstract

“…The characteristic fluorescence emission spectra of glycation products were assessed at λEx/Em = 335 nm/ 385 nm (pentosidine fluorescence) and λEx/Em = 340 nm/ 370 nm (AGEs fluorescence) and revealed significant increases at both excitation/emission wavelengths by 3 and 2.25 fold compared to unmodified BSA. The total AGEs content was evaluated using an ELISA assay (Advanced Glycation End Product ELISA Kit, Cell Biolabs, San Diego, CA, USA) which revealed that the glycated products content in AGEs-BSA increased by 3.2 fold compared to BSA, reaching 4.8 ng/μg protein [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

“…Cell membrane fractions were obtained using the RedyPrep Protein Extraction Kit (Bio-Rad Laboratories, Hercules, CA, USA) according to manufacturer’s instructions, and modified as previously described [ 41 , 42 ].…”

Section: Methodsmentioning

confidence: 99%

RAGE and TGF-β1 Cross-Talk Regulate Extracellular Matrix Turnover and Cytokine Synthesis in AGEs Exposed Fibroblast Cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

AGEs accumulation in the skin affects extracellular matrix (ECM) turnover and triggers diabetes associated skin conditions and accelerated skin aging. The receptor of AGEs (RAGE) has an essential contribution to cellular dysfunction driven by chronic inflammatory responses while TGF-β1 is critical in both dermal homeostasis and inflammation. We investigated the contribution of RAGE and TGF-β1 to the modulation of inflammatory response and ECM turnover in AGEs milieu, using a normal fibroblast cell line. RAGE, TGF-β1, collagen I and III gene and protein expression were upregulated after exposure to AGEs-BSA, and MMP-2 was activated. AGEs-RAGE was pivotal in NF-κB dependent collagen I expression and joined with TGF-β1 to stimulate collagen III expression, probably via ERK1/2 signaling. AGEs-RAGE axis induced upregulation of TGF-β1, TNF-α and IL-8 cytokines. TNF-α and IL-8 were subjected to TGF-β1 negative regulation. RAGE’s proinflammatory signaling also antagonized AGEs-TGF-β1 induced fibroblast contraction, suggesting the existence of an inhibitory cross-talk mechanism between TGF-β1 and RAGE signaling. RAGE and TGF-β1 stimulated anti-inflammatory cytokines IL-2 and IL-4 expression. GM-CSF and IL-6 expression appeared to be dependent only on TGF-β1 signaling. Our data also indicated that IFN-γ upregulated in AGEs-BSA milieu in a RAGE and TGF-β1 independent mechanism. Our findings raise the possibility that RAGE and TGF-β1 are both involved in fibrosis development in a complex cross-talk mechanism, while also acting on their own individual targets. This study contributes to the understanding of impaired wound healing associated with diabetes complications.

show abstract

“…Conditioned media samples with a total protein concentration of 800 μg/mL were used for the detection of secreted IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α cytokines using a Bio-Plex Pro Human Cytokine 8-plex panel (Bio-Rad), as previously described 10 . Secreted IL-1β was separately quantified using Bio-Plex Pro Human Cytokine Standard 27-plex, Group I, magnetic beads and detection antibodies for human IL-1β (Bio-Rad).…”

Section: Quantification Of Inflammatory Cytokines and Mmps From Concementioning

confidence: 99%

Dietary AGEs involvement in colonic inflammation and cancer: insights from an in vitro enterocyte model

Geicu

Stanca

Voicu

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

The number of colon cancer cases is increasing worldwide, and type II diabetes patients have an increased risk of developing colon cancer. Diet-borne advanced glycation end-products (AGEs) may promote neoplastic transformation; however, the mechanisms involved remain elusive. The present study helped to define the relationship between dietary AGEs and cancer progression. C2BBe1 adenocarcinoma enterocytes were exposed to 200 µg/mL glycated casein (AGEs-Csn) for up to 24 h. AGEs-Csn exposure resulted in increased cell proliferation, maladaptative changes in SOD and CAT activity and moderate levels of hydrogen peroxide (H 2 o 2 ) intracellular accumulation. AGEs-Csn activated pro-survival and proliferation signalling, such as the phosphorylation of mTOR (Ser2448) and Akt (Ser473). GSK-3β phosphorylation also increased, potentially inducing extracellular matrix remodelling and thus enabling metastasis. Moreover, AGEs-Csn induced MMP-1, -3, -7, -9 and -10 expression and activated MMP-2 and MMP-9, which are regulators of the extracellular matrix and cytokine functions. AGEs-Csn induced inflammatory responses that included extracellular IL-1β at 6 h; time-dependent increases in IL-8; RAGE and NF-κB p65 upregulation; and IκB inhibition. Co-treatment with anti-RAGE or anti-TNF-α blocking antibodies and AGEs-Csn partially counteracted these changes; however, IL-8, MMP-1 and -10 expression and MMP-9 activation were difficult to prevent. AGEs-Csn perpetuated signalling that led to cell proliferation and matrix remodelling, strengthening the link between AGEs and colorectal cancer aggressiveness.Worldwide, the annual cumulative number of deaths related to diabetes and colon cancer that were recorded in the last 20 years has increased by 90%, while in developed countries, it rose by 57%. The risk of developing colon cancer was estimated to be 27% greater in patients with type II diabetes than in those not afflicted by this disease 1 . This association is thought to be strengthened by lifestyle choices such as a diet rich in carbohydrates and advanced glycation end-products (AGEs) compounds; however, the molecular mechanisms responsible for this association remain elusive. A growing body of data has indicated that colon cancer and type II diabetes may involve shared signalling pathways, such as the activation of the inflammatory response via NF-κB, the activation of the Wnt/β-catenin pathway, iron homeostasis imbalances and increased oxidative stress 2,3 . Research has also shown that tumours tolerated higher levels of ROS than healthy tissue, most likely due to increased basal activity of antioxidative enzymes 4 . Surprisingly, this state may also be linked to increased cell proliferation and differentiation 5 and even to increased invasiveness and drug tolerance in certain tumours 6 .In cancerous cells, RAGE, which is sometimes referred to as the tumour receptor, is typically overexpressed 7-9 . The perpetuation of signalling involving the AGEs ligands, their receptor RAGE and the NF-κB transcription factor has recently been ...

show abstract

AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An Alternative Inflammatory Mechanism?

Cited by 21 publications

References 63 publications

Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis

Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis

RAGE and TGF-β1 Cross-Talk Regulate Extracellular Matrix Turnover and Cytokine Synthesis in AGEs Exposed Fibroblast Cells

Dietary AGEs involvement in colonic inflammation and cancer: insights from an in vitro enterocyte model

Contact Info

Product

Resources

About