Production and application of HMGB1 derived recombinant RAGE-antagonist peptide for anti-inflammatory therapy in acute lung injury

Lee, Seon Yeong; Piao, Chunxian; Kim, Gyeungyun; Kim, Ji Yeon; Choi, Eun‐Ji; Lee, Minhyung

doi:10.1016/j.ejps.2017.12.019

Cited by 51 publications

(34 citation statements)

References 29 publications

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“…Moreover, administration of sRAGE to RAGE −/− mice attenuated the production of inflammatory mediators, probably because sRAGE can scavenge ligands that have the potential to activate other pattern-recognition receptors such as toll-like receptor 4 30 . To our knowledge, however, our study is the first to report beneficial effects of S100P-derived RAP administration in experimental ARDS, a finding that agrees with the results from a previous study of HMGB1-derived RAP in lung-injured mice 31 .…”

Section: Discussionsupporting

confidence: 92%

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

Audard

Godet

Blondonnet

et al. 2019

Sci Rep

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The receptor for advanced glycation end-products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will require assessment of this strategy in larger animals. Forty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid (i) alone; (ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), or (iii) recombinant soluble (s)RAGE. The primary outcome was net AFC at 4 h. Arterial oxygenation was assessed hourly and alveolar-capillary permeability, alveolar inflammation and lung histology were assessed at 4 h. Treatment with either RAP or sRAGE improved net AFC (median [interquartile range], 21.2 [18.8–21.7] and 19.5 [17.1–21.5] %/h, respectively, versus 12.6 [3.2–18.8] %/h in injured, untreated controls), oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after ARDS. These findings suggest that RAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.

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Section: Discussionsupporting

confidence: 92%

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

Audard

Godet

Blondonnet

et al. 2019

Sci Rep

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show abstract

“…Moreover, administration of sRAGE to RAGE -/mice attenuated the production of inflammatory mediators, probably because sRAGE can scavenge ligands that have the potential to activate other pattern-recognition receptors such as toll-like receptor 4 [42]. To our knowledge, however, our study is the first to report beneficial effects of S100P-derived RAP administration in experimental ARDS, a finding that agrees with the results from a previous study of HMGB1-derived RAP in lung-injured mice [43].…”

Section: Discussionsupporting

confidence: 90%

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

Audard

Godet

Blondonnet

et al. 2018

Preprint

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Background:The receptor for advanced glycation end products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition was recently associated with attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will first require assessment of this strategy in larger animals.Methods: Forty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid i) alone; ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), a S100P-derived peptide that prevents activation of RAGE by its ligands, or iii) in combination with intravenous administration of recombinant soluble (s)RAGE that acted as a decoy receptor. The primary outcome measure was net AFC at 4 h. Arterial oxygenation was assessed hourly for 4 h and alveolar-capillary permeability, alveolar inflammation, lung histology and lung mRNA expression of the epithelial sodium channel (α1-ENaC), α1-Na,K-ATPase and aquaporin (AQP)-5 were assessed at 4 h. Findings: Treatment with either RAP or sRAGE improved net AFC rates (median [interquartile range], 21.2 [18.8-21.7] and 19.5 [17.1-21.5] %/h, respectively, versus 12.6 [3.2-18.8] %/h in injured, untreated controls), improved oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after acid-induced ARDS. RAGE inhibition also restored lung mRNA expression of α1-Na,K-ATPase and AQP-5. Interpretation: RAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.

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“…HMGM1, often described as the prototypical DAMP, may contribute to the development of acute or chronic lung injury by activating TLR-4, TLR-2 and RAGE receptors resulting in the activation of MAP kinases and ERK, and culminating in the nuclear translocation of NF-κB resulting in increased production of PICs and ROS [ [235] , [236] , [237] , [238] ]. Increased levels of PICs in turn induce the release of HMBG1 from immune and epithelial cells and directly cause a self-amplifying cascade of inflammation, oxidative stress and lung tissue damage [ [239] , [240] , [241] ]; (reviewed by [ 242 ]). This process is likely central to the development of chronic, escalating inflammation and tissue damage in many illnesses such as multiple sclerosis, rheumatoid arthritis and major depression and has been described as the Toll-like Receptor Radical Cycle [ 243 ].…”

Section: The Recruitment Of Activated Neutrophils Into Alveolae and Imentioning

confidence: 99%

The pathophysiology of SARS-CoV-2: A suggested model and therapeutic approach

Morris

Bortolasci

Puri³

et al. 2020

Life Sciences

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In this paper, a model is proposed of the pathophysiological processes of COVID-19 starting from the infection of human type II alveolar epithelial cells (pneumocytes) by SARS-CoV-2 and culminating in the development of ARDS. The innate immune response to infection of type II alveolar epithelial cells leads both to their death by apoptosis and pyroptosis and to alveolar macrophage activation. Activated macrophages secrete proinflammatory cytokines and chemokines and tend to polarise into the inflammatory M1 phenotype. These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space. Activated vascular endothelial cells become a source of proinflammatory cytokines and reactive oxygen species (ROS) and contribute to the development of coagulopathy, systemic sepsis, a cytokine storm and ARDS. Pulmonary activated platelets are also an important source of proinflammatory cytokines and ROS, as well as exacerbating pulmonary neutrophil-mediated inflammatory responses and contributing to systemic sepsis by binding to neutrophils to form platelet-neutrophil complexes (PNCs). PNC formation increases neutrophil recruitment, activation priming and extraversion of these immune cells into inflamed pulmonary tissue, thereby contributing to ARDS. Sequestered PNCs cause the development of a procoagulant and proinflammatory environment. The contribution to ARDS of increased extracellular histone levels, circulating mitochondrial DNA, the chromatin protein HMGB1, decreased neutrophil apoptosis, impaired macrophage efferocytosis, the cytokine storm, the toll-like receptor radical cycle, pyroptosis, necroinflammation, lymphopenia and a high Th17 to regulatory T lymphocyte ratio are detailed.

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Production and application of HMGB1 derived recombinant RAGE-antagonist peptide for anti-inflammatory therapy in acute lung injury

Cited by 51 publications

References 29 publications

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets

The pathophysiology of SARS-CoV-2: A suggested model and therapeutic approach

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