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 Accumulation of advanced glycation endproducts in patients with systemic lupus erythematosus

Rheumatology ◽  
2007 ◽  
Vol 46 (10) ◽  
pp. 1551-1556 ◽  
Author(s):  
K. de Leeuw ◽  
R. Graaff ◽  
R. de Vries ◽  
R. P. Dullaart ◽  
A. J. Smit ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Advanced Glycation Endproducts ◽  
Advanced Glycation ◽  
Systemic Lupus ◽  
Glycation Endproducts

scholarly journals The High Mobility Group (Hmg) Boxes of the Nuclear Protein Hmg1 Induce Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells

2001 ◽  
Vol 152 (6) ◽  
pp. 1197-1206 ◽  
Author(s):  
Bernard Degryse ◽  
Tiziana Bonaldi ◽  
Paola Scaffidi ◽  
Susanne Müller ◽  
Massimo Resnati ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Muscle Cells ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Cytoskeleton Reorganization ◽  
Mitogen Activated Protein

HMG1 (high mobility group 1) is a ubiquitous and abundant chromatin component. However, HMG1 can be secreted by activated macrophages and monocytes, and can act as a mediator of inflammation and endotoxic lethality. Here we document a role of extracellular HMG1 in cell migration. HMG1 (and its individual DNA-binding domains) stimulated migration of rat smooth muscle cells in chemotaxis, chemokinesis, and wound healing assays. HMG1 induced rapid and transient changes of cell shape, and actin cytoskeleton reorganization leading to an elongated polarized morphology typical of motile cells. These effects were inhibited by antibodies directed against the receptor of advanced glycation endproducts, indicating that the receptor of advanced glycation endproducts is the receptor mediating the HMG1-dependent migratory responses. Pertussis toxin and the mitogen-activated protein kinase kinase inhibitor PD98059 also blocked HMG1-induced rat smooth muscle cell migration, suggesting that a Gi/o protein and mitogen-activated protein kinases are required for the HMG1 signaling pathway. We also show that HMG1 can be released by damage or necrosis of a variety of cell types, including endothelial cells. Thus, HMG1 has all the hallmarks of a molecule that can promote atherosclerosis and restenosis after vascular damage.

scholarly journals High-Mobility Group Protein Box-1 and its Relevance to Cerebral Ischemia

2009 ◽  
Vol 30 (2) ◽  
pp. 243-254 ◽  
Author(s):  
Qing-Wu Yang ◽  
Jing-Zhou Wang ◽  
Jing-Cheng Li ◽  
Yu Zhou ◽  
Qi-Zhong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
High Mobility Group ◽  
High Mobility Group Protein ◽  
Glycation Endproducts ◽  
Extracellular Milieu ◽  
Proinflammatory Mediators ◽  
Group Protein ◽  
Therapeutic Tools

High-mobility group box-1 (HMGB1) was originally identified as a ubiquitously expressed, abundant, nonhistone DNA-binding protein. It has well-established functions in the maintenance of nuclear homeostasis. The HMGB1 can either be passively released into the extracellular milieu in response to necrotic signals or actively secreted in response to inflammatory signals. Extracellular HMGB1 interacts with receptors, including those for advanced glycation endproducts (RAGEs) as well as Toll-like receptor 2 (TLR2) and TLR4. The HMGB1 functions in a synergistic manner with other proinflammatory mediators and acts as a potent proinflammatory cytokine-like factor that contributes to the pathogenesis of diverse inflammatory and infectious disorders. Numerous reports point to HMGB1 as a novel player in the ischemic brain. This review provides an appraisal of the emerging roles of HMGB1 in cerebral ischemia injury, highlighting the relevance of HMGB1-blocking agents as potent therapeutic tools for neuroprotection.

scholarly journals Role of Moesin Phosphorylation in Retinal Pericyte Migration and Detachment Induced by Advanced Glycation Endproducts

2020 ◽  
Vol 11 ◽  
Author(s):  
Shuang-Shuang Zhang ◽  
Jia-Qing Hu ◽  
Xiao-Hui Liu ◽  
Li-Xian Chen ◽  
Hong Chen ◽  
...  
Keyword(s):  
Advanced Glycation Endproducts ◽  
Advanced Glycation ◽  
Glycation Endproducts

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.

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