scholarly journals Pseudomonas aeruginosa significantly increases expression of receptor for advanced glycation endproducts (RAGE) in the septicemia suffering patients

2021 ◽  
Vol 11 (5) ◽  
pp. 984-988
Author(s):  
A. Kariminik ◽  
F. Hosseini ◽  
E. Nasiri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Immune Responses ◽  
Advanced Glycation Endproducts ◽  
Cell Surface Receptor ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Surface Receptor ◽  
A Cell

Receptor for Advanced Glycation Endproducts (RAGE) is a cell surface receptor, which recognizes several endogenous and exogenous molecules and subsequently induces expression of several molecules including chemokines. Chemokines are members of the cytokine superfamily and participate in several immune system functions, including cell migration, inflammation, angiogenesis/angiostasis etc. CXC ligand 11 (CXCL11) is an important chemokine which participates in the induction of appropriate immune responses against microbes, including bacteria. The main mechanisms responsible to overcome septicemia are yet to be clarified. Thus, it has been hypothesized that RAGE may participate in induction of CXCL11 in response to the microbial agents. Due to the fact that immune responses play key roles in limitation of infection, it has been proposed that RAGE may inhibit spread of septicemia. Therefore, in this project mRNA levels of RAGE and CXCL11 were explored in the patients suffering from septicemia versus healthy controls. RAGE and CXCL11 expression levels in the 80 subjects, including 40 septicemia patients and 40 healthy controls were explored using Real-Time PCR technique. Accordingly, by using the specific primer against RAGE and CXCL11 in a Rotorgene vehicle the mRNA levels have been determined. The septicemia and the sources of the bacteria in the blood were diagnosed using microbial cultures. The results demonstrated that although mRNA levels for RAGE and CXCL11 did not change in the septicemia patients vs. healthy controls, mRNA levels of RAGE were significantly higher in the patients infected by Pseudomonas aeruginosa compared to those infected by other bacteria, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii. RAGE and CXCL11 mRNA levels did not differ among male and female patients. Based on the results it seems that RAGE is a critical receptor against P. aeruginosa during septicemia and more investigations, especially on the RAGE down-stream molecules can clarify its main roles against P. aeruginosa.

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.

scholarly journals Noninvasive Measurement of Skin Autofluorescence Is Increased in Patients with Systemic Sclerosis: An Indicator of Increased Advanced Glycation Endproducts?

2012 ◽  
Vol 39 (8) ◽  
pp. 1654-1658 ◽  
Author(s):  
ANDREA K. MURRAY ◽  
TONIA L. MOORE ◽  
JOANNE B. MANNING ◽  
CHRISTOPHER E.M. GRIFFITHS ◽  
ARIANE L. HERRICK
Keyword(s):  
Oxidative Stress ◽  
Systemic Sclerosis ◽  
Upper Limb ◽  
Advanced Glycation Endproducts ◽  
Proximal Phalanx ◽  
Healthy Controls ◽  
Skin Autofluorescence ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Primary Raynaud’S Phenomenon

Objective.Skin autofluorescence noninvasively assesses expression of advanced glycation endproducts and therefore potentially the presence of oxidative stress that is implicated in the pathogenesis of systemic sclerosis (SSc). We investigated whether autofluorescence was increased in patients with SSc, primary Raynaud’s phenomenon (RP), and morphea as compared to healthy controls.Methods.Measurements of autofluorescence were made at 5 upper limb sites in 16 healthy controls, 16 patients with diffuse cutaneous SSc (dcSSc), 15 with limited cutaneous SSc (lcSSc), 15 with primary RP, and 13 with morphea. For patients with morphea, additional measurements were made at the affected and an adjacent unaffected site.Results.Autofluorescence was significantly increased in patients with dcSSc but not lcSSc as compared to controls at the proximal phalanx [dcSSc median 0.15, interquartile range (IQR) 0.10–0.24, vs control 0.10, IQR 0.07–0.13; p = 0.014], dorsum of the hand (dcSSc 0.17, IQR 0.11–0.36, vs control 0.12, IQR 0.09–0.17; p = 0.031), the wrist (dcSSc 0.22, IQR 0.13–0.33, vs control 0.13, IQR 0.09–0.18; p = 0.005), and forearm (dcSSc 0.19, IQR 0.12–0.47, vs control 0.14, IQR 0.10–0.16; p = 0.022). There was a trend for autofluorescence to be increased in patients with lcSSc and at morphea sites, compared to noninvolved skin.Conclusion.Autofluorescence is increased in patients with dcSSc compared to primary RP and to healthy controls. This suggests increased oxidative stress and the potential for autofluorescence as a biomarker.

scholarly journals Involvement of Receptor for Advanced Glycation Endproducts in Hypertensive Disorders of Pregnancy

2019 ◽  
Vol 20 (21) ◽  
pp. 5462 ◽  
Author(s):  
Akasaka ◽  
Naruse ◽  
Sado ◽  
Uchiyama ◽  
Makino ◽  
...  
Keyword(s):  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Mrna Levels ◽  
Hypertensive Disorders Of Pregnancy ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Hypertensive Disorders ◽  
Chemokine Ligand ◽  
Life Threatening ◽  
Interfering Rna

Preeclampsia/hypertensive disorders of pregnancy (PE/HDP) is a serious and potentially life-threatening disease. Recently, PE/HDP has been considered to cause adipose tissue inflammation, but the detailed mechanism remains unknown. We exposed human primary cultured adipocytes with serum from PE/HDP and healthy controls for 24 h, and analyzed mRNA expression of several adipokines, cytokines, and ligands of the receptor for advanced glycation endproducts (RAGE). We found that the mRNA levels of interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), high mobility group box 1 (HMGB1), and RAGE were significantly increased by the addition of PE/HDP serum. Among RAGE ligands, advanced glycation endproducts (AGE) and HMGB1 increased mRNA levels of IL-6 and CCL2 in SW872 human adipocytes and mouse 3T3-L1 cells. The introduction of small interfering RNA for RAGE (siRAGE) into SW872 cells abolished the AGE- and HMGB1-induced up-regulation of IL-6 and CCL2. In addition, lipopolysaccharide (LPS), a ligand of RAGE, increased the expression of IL-6 and CCL2 and siRAGE attenuated the LPS-induced expression of IL-6 and CCL2. These results strongly suggest that the elevated AGE, HMGB1, and LPS in pregnant women up-regulate the expression of IL-6 and CCL2 via the RAGE system, leading to systemic inflammation such as PE/HDP.

Soluble Receptor for Advanced Glycation Endproducts Is Decreased in Patients with Juvenile Idiopathic Arthritis (ERA Category) and Inversely Correlates with Disease Activity and S100A12 Levels

2011 ◽  
Vol 38 (9) ◽  
pp. 1994-1999 ◽  
Author(s):  
ARPITA MYLES ◽  
VISHAD VISWANATH ◽  
YOGESH PREET SINGH ◽  
AMITA AGGARWAL
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Advanced Glycation Endproducts ◽  
Tender Joint Count ◽  
Healthy Controls ◽  
Advanced Glycation ◽  
Tender Joint ◽  
Glycation Endproducts ◽  
Paired Samples ◽  
Soluble Rage

Objective.Membrane-bound receptor for advanced glycation endproducts (mRAGE) is overexpressed in response to increasing concentrations of its ligand (e.g., S100A12) and triggers an inflammatory immune response. In contrast, soluble RAGE (sRAGE) acts as a decoy receptor and downmodulates inflammation. Decreased sRAGE levels are associated with autoimmune diseases; however, limited data are available in juvenile idiopathic arthritis (JIA). We studied sRAGE levels in patients with JIA [enthesitis-related arthritis (ERA) category].Methods.sRAGE levels were estimated in the serum of patients with ERA JIA (n = 101), systemic-onset JIA and polyarticular JIA (n = 10 each), and healthy controls (n = 45). Synovial fluid (SF) sRAGE was measured in patients with ERA, rheumatoid arthritis, reactive arthritis, and osteoarthritis (n = 10). Levels of S100A12 were also measured. Twenty-four patients with ERA were followed for 4 months. Disease activity was assessed by swollen joint count (SJC), tender joint count (TJC), and erythrocyte sedimentation rate (ESR). All levels are expressed as median (range).Results.The serum sRAGE (pg/ml) level was significantly lower in patients compared to healthy controls [515 (64–1887) vs 1542 (627–3159); p < 0.0001]. In paired samples, SF had lower levels compared to corresponding plasma level [102 (51–799) vs 481 (134–1006); p < 0.0001]. The level of S100A12 (ng/ml) was higher in SF (1042; 573–1415) than serum (638; 208–779). Serum sRAGE correlated negatively with S100A12 levels (r = −0.474; p < 0.01.), ESR (r = −0.306; p < 0.01), and SJC (r = −0.237; p < 0.05), but not with TJC (r = −0.134; p = NS). The levels of sRAGE remained stable over time in patients with stable disease.Conclusion.Levels of sRAGE are reduced in patients with ERA and correlate negatively with disease activity and S100A12 levels. sRAGE may be a modulator of inflammation in these patients.

Inhibition of RAGE Axis Signaling: A Pharmacological Challenge

2019 ◽  
Vol 20 (3) ◽  
pp. 340-346 ◽  
Author(s):  
Armando Rojas ◽  
Miguel Morales ◽  
Ileana Gonzalez ◽  
Paulina Araya
Keyword(s):  
Cell Surface Receptor ◽  
Clinical Settings ◽  
Advanced Glycation ◽  
Binding Domains ◽  
Pharmacological Challenge ◽  
Glycation End Products ◽  
End Products ◽  
Attractive Therapeutic Target ◽  
Surface Receptor ◽  
Recognition Receptor

The Receptor for Advanced Glycation End Products (RAGE) is an important cell surface receptor, which belongs to the IgG super family and is now considered as a pattern recognition receptor. Because of its relevance in many human clinical settings, it is now pursued as a very attractive therapeutic target. However, particular features of this receptor such as a wide repertoire of ligands with different binding domains, the existence of many RAGE variants as well as the presence of cytoplasmatic adaptors leading a diverse signaling, are important limitations in the search for successful pharmacological approaches to inhibit RAGE signaling. Therefore, the present review aimed to display the most promising approaches to inhibit RAGE signaling, and provide an up to date review of progress in this area.

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