A Systematic Nomenclature for the Redox States of High Mobility Group Box (HMGB) Proteins

Antoine, Daniel J.; Harris, Helena Erlandsson; Andersson, Ulf; Tracey, Kevin J.; Bianchi, Marco E.

doi:10.2119/molmed.2014.00022

Cited by 95 publications

(75 citation statements)

References 10 publications

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“…Receptor specificity is only partially understood but is known to involve the redox status of HMGB1 as well as extraceullar- and intracellular-binding partners. 40 For example, when all 3 cysteines, C23, C45, and C106, within HMGB1 are in the thiol configuration extracellular HMGB1 avidly interacts with C–X–C motif chemokine (CXCL)12 and activates signaling through CXCR4. 24 Mild oxidation of this form leads to formation of a disulfide bond between C23 and C45 and it is this isoform that binds to MD2 to trigger TLR4 signaling.…”

Section: Discussionmentioning

confidence: 99%

HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4

Cai

Yuan

Wang

et al. 2015

ATVB

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Objective Endoluminal vascular interventions such as angioplasty initiate a sterile inflammatory response resulting from local tissue damage. This response drives the development of intimal hyperplasia (IH) that, in turn, can lead to arterial occlusion. We hypothesized that the ubiquitous nuclear protein and damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1), is one of the endogenous mediators that activates processes leading to IH after endoluminal injury to the arterial wall. The aim of this study is to investigate whether approaches that reduce the levels of HMGB1 or inhibit its activity suppresses IH after arterial injury. Approach and Results Here, we show that HMGB1 regulates IH in a mouse carotid wire injury model. Induced genetic deletion or neutralization of HMGB1 prevents IH, monocyte recruitment, and smooth muscle cell growth factor production after endoluminal carotid artery injury. A specific inhibitor of HMGB1 myeloid differentiation factor 2–toll-like receptor 4 (TLR4) interaction, P5779, also significantly inhibits IH. HMGB1 deletion is mimicked in this model by global deletion of TLR4 and partially replicated by myeloid-specific deletion of TLR4 but not TLR2 or receptor for advanced glycation endproducts deletion. The specific HMGB1 isoform known to activate TLR4 signaling (disulfide HMGB1) stimulates smooth muscle cell to migrate and produce monocyte chemotactic protein 1/CCL2) via TLR4. Macrophages produce smooth muscle cell mitogens in response to disulfide HMGB1 also in a TLR4/myeloid differentiation primary response gene (88)/Trif-dependent manner. Conclusions These findings place HMGB1 and its receptor, TLR4 as critical regulators of the events that drive the inflammation leading to IH after endoluminal arterial injury and identify this pathway as a possible therapeutic target to limit IH to attenuate damage-associated molecular pattern molecule–mediated vascular inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4

Cai

Yuan

Wang

et al. 2015

ATVB

Self Cite

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“…The different HMGB1 redox forms can be identified in serum, saliva, and cell culture medium by mass spectrometry (Balosso et al, 2014; Liu et al, 2012a; Schiraldi et al, 2012; Venereau et al, 2012; Yang et al, 2010a) and nuclear magnetic resonance (NMR) spectroscopy (Zandarashvili et al, 2013), although currently there is no convenient method. A systematic nomenclature for the redox states of HMGB1 and other HMGB proteins has been proposed by Marco E. Bianchi and colleagues (Antoine et al, 2014). …”

Section: Hmgb1 Post-translational Modificationmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

802

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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“…The pro-inflammatory form occurs under increased oxidizing conditions, in which a disulfide bridge forms between C23 and C45 (disulfide (ds) HMGB-1). This redox form interacts with TLR4 to induce synthesis and secretion of pro-inflammatory cytokines (Antoine et al., 2014). Finally, the fully oxidized form of HMGB-1 has no known biological activity (Venereau et al., 2012).…”

Section: Neuroinflammatory Processes and Microgliamentioning

confidence: 99%

Stress-induced neuroinflammatory priming: A liability factor in the etiology of psychiatric disorders

Frank

Weber

Watkins

et al. 2016

Neurobiology of Stress

111

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Stress and glucocorticoids (GCs) have universally been considered to be anti-inflammatory, however in recent years, stress and GCs have been found to exert permissive effects (immunological priming) on neuroinflammatory processes. This phenomenon of priming is characterized by prior stress or GC exposure potentiating the neuroinflammatory response to a subsequent immune challenge. A considerable body of evidence is discussed here that supports this permissive effect of stress and GCs.In light of this evidence, a mechanism of neuroinflammatory priming is proposed involving a signal cascade in the brain involving danger-associated molecular patterns (HMGB-1) and inflammasomes (NLRP3), which results in an exaggerated or amplified neuroinflammatory response and subsequently, the amplification of the physiological and behavioral sequelae of this response (i.e. sickness). Finally, we explore the notion that stressor-induced sensitization of the neuroimmune microenvironment may predispose individuals to psychiatric disorders, in which exaggerated innate immune/inflammatory responses in the brain are now thought to play a key role.

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A Systematic Nomenclature for the Redox States of High Mobility Group Box (HMGB) Proteins

Cited by 95 publications

References 10 publications

HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4

HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4

HMGB1 in health and disease

Stress-induced neuroinflammatory priming: A liability factor in the etiology of psychiatric disorders

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