Cells

Editorial

Jump to: Research, Review

3 pages, 181 KiB

Open AccessEditorial

Regulation of HMGB1 Release in Health and Diseases

by Haichao Wang

Cells 2023, 12(1), 46; https://doi.org/10.3390/cells12010046 - 22 Dec 2022

Cited by 3 | Viewed by 1134

Abstract

Almost a half century ago, a group of nuclear proteins were co-purified with histones from calf thymus and termed as “high mobility group” (HMG) proteins because of their relative rapid mobility on SDS-PAGE gels [...] Full article

(This article belongs to the Special Issue Regulation of HMGB1 Release in Health and Diseases)

Research

Jump to: Editorial, Review

19 pages, 5219 KiB

Open AccessArticle

Inhibition of Cochlear HMGB1 Expression Attenuates Oxidative Stress and Inflammation in an Experimental Murine Model of Noise-Induced Hearing Loss

by Cheng-Ping Shih, Chao-Yin Kuo, Yuan-Yung Lin, Yi-Chun Lin, Hang-Kang Chen, Hao Wang, Hsin-Chien Chen and Chih-Hung Wang

Cells 2021, 10(4), 810; https://doi.org/10.3390/cells10040810 - 05 Apr 2021

Cited by 16 | Viewed by 2654

Abstract

Noise-induced hearing loss (NIHL) is a common inner ear disease but has complex pathological mechanisms, one of which is increased oxidative stress in the cochlea. The high-mobility group box 1 (HMGB1) protein acts as an inflammatory mediator and shows different activities with redox [...] Read more.

Noise-induced hearing loss (NIHL) is a common inner ear disease but has complex pathological mechanisms, one of which is increased oxidative stress in the cochlea. The high-mobility group box 1 (HMGB1) protein acts as an inflammatory mediator and shows different activities with redox modifications linked to the generation of reactive oxygen species (ROS). We aimed to investigate whether manipulation of cochlear HMGB1 during noise exposure could prevent noise-induced oxidative stress and hearing loss. Sixty CBA/CaJ mice were divided into two groups. An intraperitoneal injection of anti-HMGB1 antibodies was administered to the experimental group; the control group was injected with saline. Thirty minutes later, all mice were subjected to white noise exposure. Subsequent cochlear damage, including auditory threshold shifts, hair cell loss, expression of cochlear HMGB1, and free radical activity, was then evaluated. The levels of HMGB1 and 4-hydroxynonenal (4-HNE), as respective markers of reactive nitrogen species (RNS) and ROS formation, showed slight increases on post-exposure day 1 and achieved their highest levels on post-exposure day 4. After noise exposure, the antibody-treated mice showed markedly less ROS formation and lower expression of NADPH oxidase 4 (NOX4), nitrotyrosine, inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1) than the saline-treated control mice. A significant amelioration was also observed in the threshold shifts of the auditory brainstem response and the loss of outer hair cells in the antibody-treated versus the saline-treated mice. Our results suggest that inhibition of HMGB1 by neutralization with anti-HMGB1 antibodies prior to noise exposure effectively attenuated oxidative stress and subsequent inflammation. This procedure could therefore have potential as a therapy for NIHL. Full article

(This article belongs to the Special Issue Regulation of HMGB1 Release in Health and Diseases)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

21 pages, 1379 KiB

Open AccessReview

HMGB1-Mediated Activation of the Inflammatory-Reparative Response Following Myocardial Infarction

by Eleonora Foglio, Laura Pellegrini, Matteo Antonio Russo and Federica Limana

Cells 2022, 11(2), 216; https://doi.org/10.3390/cells11020216 - 10 Jan 2022

Cited by 12 | Viewed by 3358

Abstract

Different cell types belonging to the innate and adaptive immune system play mutually non-exclusive roles during the different phases of the inflammatory-reparative response that occurs following myocardial infarction. A timely and finely regulation of their action is fundamental for the process to properly [...] Read more.

Different cell types belonging to the innate and adaptive immune system play mutually non-exclusive roles during the different phases of the inflammatory-reparative response that occurs following myocardial infarction. A timely and finely regulation of their action is fundamental for the process to properly proceed. The high-mobility group box 1 (HMGB1), a highly conserved nuclear protein that in the extracellular space can act as a damage-associated molecular pattern (DAMP) involved in a large variety of different processes, such as inflammation, migration, invasion, proliferation, differentiation, and tissue regeneration, has recently emerged as a possible regulator of the activity of different immune cell types in the distinct phases of the inflammatory reparative process. Moreover, by activating endogenous stem cells, inducing endothelial cells, and by modulating cardiac fibroblast activity, HMGB1 could represent a master regulator of the inflammatory and reparative responses following MI. In this review, we will provide an overview of cellular effectors involved in these processes and how HMGB1 intervenes in regulating each of them. Moreover, we will summarize HMGB1 roles in regulating other cell types that are involved in the different phases of the inflammatory-reparative response, discussing how its redox status could affect its activity. Full article

(This article belongs to the Special Issue Regulation of HMGB1 Release in Health and Diseases)

► Show Figures

Figure 1

10 pages, 1296 KiB

Open AccessReview

Neurons Are a Primary Driver of Inflammation via Release of HMGB1

by Huan Yang, Ulf Andersson and Michael Brines

Cells 2021, 10(10), 2791; https://doi.org/10.3390/cells10102791 - 18 Oct 2021

Cited by 13 | Viewed by 2929

Abstract

Recent data show that activation of nociceptive (sensory) nerves turns on localized inflammation within the innervated area in a retrograde manner (antidromically), even in the absence of tissue injury or molecular markers of foreign invaders. This neuroinflammatory process is activated and sustained by [...] Read more.

Recent data show that activation of nociceptive (sensory) nerves turns on localized inflammation within the innervated area in a retrograde manner (antidromically), even in the absence of tissue injury or molecular markers of foreign invaders. This neuroinflammatory process is activated and sustained by the release of neuronal products, such as neuropeptides, with the subsequent amplification via recruitment of immunocompetent cells, including macrophages and lymphocytes. High mobility group box 1 protein (HMGB1) is a highly conserved, well characterized damage-associated molecular pattern molecule expressed by many cells, including nociceptors and is a marker of inflammatory diseases. In this review, we summarize recent evidence showing that neuronal HMGB1 is required for the development of neuroinflammation, as knock out limited to neurons or its neutralization via antibodies ameliorate injury in models of nerve injury and of arthritis. Further, the results of study show that HMGB1 is actively released during neuronal depolarization and thus plays a previously unrecognized key etiologic role in the initiation and amplification of neuroinflammation. Direct targeting of HMGB1 is a promising approach for novel anti-inflammatory therapy. Full article

(This article belongs to the Special Issue Regulation of HMGB1 Release in Health and Diseases)

► Show Figures

Figure 1

17 pages, 2200 KiB

Open AccessReview

High-Mobility Group Box-1 and Its Potential Role in Perioperative Neurocognitive Disorders

by Sarah Saxena, Véronique Kruys, Raf De Jongh, Joseph Vamecq and Mervyn Maze

Cells 2021, 10(10), 2582; https://doi.org/10.3390/cells10102582 - 28 Sep 2021

Cited by 10 | Viewed by 2866

Abstract

Aseptic surgical trauma provokes the release of HMGB1, which engages the innate immune response after binding to pattern-recognition receptors on circulating bone marrow-derived monocytes (BM-DM). The initial systemic inflammation, together with HMGB1, disrupts the blood–brain barrier allowing penetration of CCR2-expressing BM-DMs into the [...] Read more.

Aseptic surgical trauma provokes the release of HMGB1, which engages the innate immune response after binding to pattern-recognition receptors on circulating bone marrow-derived monocytes (BM-DM). The initial systemic inflammation, together with HMGB1, disrupts the blood–brain barrier allowing penetration of CCR2-expressing BM-DMs into the hippocampus, attracted by the chemokine MCP-1 that is upregulated by HMGB1. Within the brain parenchyma quiescent microglia are activated and, together with the translocated BM-DMs, release proinflammatory cytokines that disrupt synaptic plasticity and hence memory formation and retention, resulting in postoperative cognitive decline (PCD). Neutralizing antibodies to HMGB1 prevents the inflammatory response to trauma and PCD. Full article

(This article belongs to the Special Issue Regulation of HMGB1 Release in Health and Diseases)

► Show Figures

Figure 1

20 pages, 1841 KiB

Open AccessReview

Endogenous Regulation and Pharmacological Modulation of Sepsis-Induced HMGB1 Release and Action: An Updated Review

by Cassie Shu Zhu, Wei Wang, Xiaoling Qiang, Weiqiang Chen, Xiqian Lan, Jianhua Li and Haichao Wang

Cells 2021, 10(9), 2220; https://doi.org/10.3390/cells10092220 - 27 Aug 2021

Cited by 14 | Viewed by 4812

Abstract

Sepsis remains a common cause of death in intensive care units, accounting for approximately 20% of total deaths worldwide. Its pathogenesis is partly attributable to dysregulated inflammatory responses to bacterial endotoxins (such as lipopolysaccharide, LPS), which stimulate innate immune cells to sequentially release [...] Read more.

Sepsis remains a common cause of death in intensive care units, accounting for approximately 20% of total deaths worldwide. Its pathogenesis is partly attributable to dysregulated inflammatory responses to bacterial endotoxins (such as lipopolysaccharide, LPS), which stimulate innate immune cells to sequentially release early cytokines (such as tumor necrosis factor (TNF) and interferons (IFNs)) and late mediators (such as high-mobility group box 1, HMGB1). Despite difficulties in translating mechanistic insights into effective therapies, an improved understanding of the complex mechanisms underlying the pathogenesis of sepsis is still urgently needed. Here, we review recent progress in elucidating the intricate mechanisms underlying the regulation of HMGB1 release and action, and propose a few potential therapeutic candidates for future clinical investigations. Full article

(This article belongs to the Special Issue Regulation of HMGB1 Release in Health and Diseases)

► Show Figures

Figure 1

26 pages, 2082 KiB

Open AccessReview

The Effect and Regulatory Mechanism of High Mobility Group Box-1 Protein on Immune Cells in Inflammatory Diseases

by Yun Ge, Man Huang and Yong-ming Yao

Cells 2021, 10(5), 1044; https://doi.org/10.3390/cells10051044 - 28 Apr 2021

Cited by 35 | Viewed by 4167

Abstract

High mobility group box-1 protein (HMGB1), a member of the high mobility group protein superfamily, is an abundant and ubiquitously expressed nuclear protein. Intracellular HMGB1 is released by immune and necrotic cells and secreted HMGB1 activates a range of immune cells, contributing to [...] Read more.

High mobility group box-1 protein (HMGB1), a member of the high mobility group protein superfamily, is an abundant and ubiquitously expressed nuclear protein. Intracellular HMGB1 is released by immune and necrotic cells and secreted HMGB1 activates a range of immune cells, contributing to the excessive release of inflammatory cytokines and promoting processes such as cell migration and adhesion. Moreover, HMGB1 is a typical damage-associated molecular pattern molecule that participates in various inflammatory and immune responses. In these ways, it plays a critical role in the pathophysiology of inflammatory diseases. Herein, we review the effects of HMGB1 on various immune cell types and describe the molecular mechanisms by which it contributes to the development of inflammatory disorders. Finally, we address the therapeutic potential of targeting HMGB1. Full article

(This article belongs to the Special Issue Regulation of HMGB1 Release in Health and Diseases)

► Show Figures

Figure 1

14 pages, 1132 KiB

Open AccessReview

The Immune Tolerance Role of the HMGB1-RAGE Axis

by Haruki Watanabe and Myoungsun Son

Cells 2021, 10(3), 564; https://doi.org/10.3390/cells10030564 - 05 Mar 2021

Cited by 36 | Viewed by 5801

Abstract

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. [...] Read more.

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. Full article

(This article belongs to the Special Issue Regulation of HMGB1 Release in Health and Diseases)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Regulation of HMGB1 Release in Health and Diseases

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (8 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI