scholarly journals Antagonism of Cerebral High Mobility Group Box 1 Ameliorates Dendritic Cell Dysfunction in Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Ren ◽  
Ren-qi Yao ◽  
Li-xue Wang ◽  
Jun-cong Li ◽  
Kun-wei Chen ◽  
...  
Keyword(s):  
Immune Cells ◽  
Cholinergic System ◽  
Gene Knockout ◽  
High Mobility ◽  
High Mobility Group ◽  
Inhibitory Effects ◽  
Mhc Ii ◽  
Cell Dysfunction ◽  
Global Health Issue ◽  
Specific Antagonist

Sepsis has emerged as a global health issue, and accounts for millions of deaths in intensive care units. Dysregulation of the immune response reportedly contributes to the pathogenesis and progression of this lethal condition, which involves both the dysfunction of immune cells and incompetent immunomodulatory mechanisms. High mobility group box 1 (HMGB1) is known as a later inflammatory mediator and is critically involved in the severity and prognosis of sepsis by inducing intractable inflammation and dysfunction of various immune cells. In the present study, we found that intracerebroventricular (ICV) injection of Box A, a specific antagonist of HMGB1, restored the dysregulated response of splenic dendritic cells (DCs) in septic mice by enhancing the expression of surface molecules, including CD80, CD86, and MHC-II, as well as improving DC priming of T lymphocytes. Cerebral HMGB1 was also confirmed to have potent inhibitory effects on DC functions when administrated by ICV injection in normal mice. The brain cholinergic system was found to mediate the immunomodulatory effects of central HMGB1, as it exhibited enhanced activity with persistent HMGB1 exposure. Furthermore, the inhibitory effects of cerebral HMGB1 on the response of peripheral DCs were also blocked by α7nAchR gene knockout. These findings provide novel insight into the relationship between cerebral HMGB1 and splenic DC dysfunction during sepsis, which is, at least in part, dependent on cholinergic system activity.

High Mobility Group Box 1: An Immune-regulatory Protein

2019 ◽  
Vol 19 (2) ◽  
pp. 100-109 ◽  
Author(s):  
Jingjing Zhao ◽  
Tianle Sun ◽  
Shengdi Wu ◽  
Yufeng Liu
Keyword(s):  
Inflammatory Response ◽  
Transcription Regulation ◽  
Tissue Regeneration ◽  
Cell Nucleus ◽  
Immune Cells ◽  
Inflammatory Diseases ◽  
Regulatory Protein ◽  
High Mobility ◽  
High Mobility Group ◽  
Almost All

High mobility group box 1 (HMGB1) presents in almost all somatic cells as a component of the cell nucleus. It is necessary for transcription regulation during cell development. Recent studies indicate that extracellular HMGB1, coming from necrotic cells or activated immune cells, triggers inflammatory response whereas intracellular HMGB1 controls the balance between autophagy and apoptosis. In addition, reduced HMGB1 can effectively mediate tissue regeneration. HMGB1, therefore, is regarded as a therapeutic target for inflammatory diseases. In this review, we summarized and discussed the immunomodulatory effect of HMGB1.

scholarly journals High Mobility Group Protein 1 Reverses Immune System Paralysis in Late-Phase Sepsis

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
Qing-yang Liu ◽  
Yue-Xin Wang ◽  
Zong-Sheng Wu ◽  
Zhen-wei Shi ◽  
Xu Wu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Bone Marrow Cells ◽  
Late Phase ◽  
Cecal Ligation ◽  
High Mobility ◽  
High Mobility Group ◽  
Infection Model ◽  
Inflammatory Factor ◽  
High Mobility Group Protein ◽  
Group Protein

ABSTRACTHigh mobility group protein 1 (HMGB1) is considered to be the primary inflammatory factor triggering immune paralysis in late-phase sepsis. In this study, however, we wanted to explore the possibility of using HMGB1 to boost local differentiation of bone marrow cells (BMCs) into regulatory dendritic cells (DCs)in vivo, thereby inducing immune reversal in late-phase sepsis and improving the prognosis. For this purpose, sepsis was induced by cecal ligation and puncture (CLP). Mice were injected intraperitoneally with HMGB1 (10, 50, or 250 μg/kg of body weight) 7 days before CLP. BMCs and liver immune cells were isolated at 0, 3, 5, and 7 days post-CLP. Mice were intranasally infected withPseudomonas aeruginosa3 days post-CLP as a secondary pneumonia infection model. BMCs and liver cells isolated from septic mice pretreated with HMGB1 were adoptively transferred into CLP mice. GFP+-C57BL/6 and C3H/HeN-C3H/HeJ parabiosis models were established. We found that HMGB1 pretreatment improved the survival of sepsis and increased the numbers of BMCs and liver immune cells in CLP mice. Furthermore, HMGB1 stimulation improved survival in the secondary pneumonia infection model. HMGB1 increased the number as well as the percentage of CD11c−CD45RBhighDCs in septic BM and liver. Adoptive transfer of septic cells pretreated with HMGB1 into CLP mice attenuated sepsis. HMGB1 enhanced the redistribution of CD11c−CD45RBhighDCs through TLR4 signaling in parabiosis models. We conclude that HMGB1 triggers immune reversal through the mobilization, redistribution, and local immune differentiation of BMCs, thereby compensating for impaired immunity and leading to sufficient bacterial eradication.

scholarly journals Adsorption of the Inflammatory Mediator High-Mobility Group Box 1 by Polymers with Different Charge and Porosity

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Carla Tripisciano ◽  
Tanja Eichhorn ◽  
Stephan Harm ◽  
Viktoria Weber
Keyword(s):  
Immune Cells ◽  
Physicochemical Parameters ◽  
Plasma Proteins ◽  
Mononuclear Cells ◽  
Inflammatory Mediator ◽  
High Mobility ◽  
High Mobility Group ◽  
Biological Functions ◽  
Potential Therapeutic Target ◽  
Peripheral Blood Mononuclear

High-mobility group box 1 protein (HMGB1) is a conserved protein with a variety of biological functions inside as well as outside the cell. When released by activated immune cells, it acts as a proinflammatory cytokine. Its delayed release has sparked the interest in HMGB1 as a potential therapeutic target. Here, we studied the adsorption of HMGB1 to anionic methacrylate-based polymers as well as to neutral polystyrene-divinylbenzene copolymers. Both groups of adsorbents exhibited efficient binding of recombinant HMGB1 and of HMGB1 derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells. The adsorption characteristics depended on particle size, porosity, accessibility of the pores, and charge of the polymers. In addition to these physicochemical parameters of the adsorbents, modifications of the molecule itself (e.g., acetylation, phosphorylation, and oxidation), interaction with other plasma proteins or anticoagulants (e.g., heparin), or association with extracellular microvesicles may influence the binding of HMGB1 to adsorbents and lead to preferential depletion of HMGB1 subsets with different biological activity.

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

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1044
Author(s):  
Yun Ge ◽  
Man Huang ◽  
Yong-ming Yao
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
High Mobility ◽  
Cell Types ◽  
High Mobility Group ◽  
High Mobility Group Protein

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.

Luteolin attenuates hepatic injury in septic mice by regulating P2x7R-based HMGB1 release

2021 ◽  
Author(s):  
Zhi-Hong Zhang ◽  
Hong-Xu Yang ◽  
Quan Jin ◽  
Yan-Ling Wu ◽  
Zhen-Yu Cui ◽  
...  
Keyword(s):  
Immune Cells ◽  
P2x7 Receptor ◽  
Hepatic Injury ◽  
High Mobility ◽  
High Mobility Group

P2x7 receptor (P2x7R) and NLRP3 cooperatively participate in the inflammation and hepatocytes damage during hepatic injury induced by lipopolysaccharide (LPS). High-mobility group box 1 (HMGB1) released from immune cells in...

scholarly journals Pretreatment with High Mobility Group Box-1 Monoclonal Antibody Prevents the Onset of Trigeminal Neuropathy in Mice with a Distal Infraorbital Nerve Chronic Constriction Injury

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2035
Author(s):  
Takahiro Kochi ◽  
Yoki Nakamura ◽  
Simeng Ma ◽  
Kazue Hisaoka-Nakashima ◽  
Dengli Wang ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Trigeminal Nerve ◽  
Immune Cells ◽  
Cell Activation ◽  
Chronic Constriction Injury ◽  
Immune Cell ◽  
Tissue Injury ◽  
High Mobility ◽  
High Mobility Group ◽  
Infraorbital Nerve

Persistent pain following orofacial surgery is not uncommon. High mobility group box 1 (HMGB1), an alarmin, is released by peripheral immune cells following nerve injury and could be related to pain associated with trigeminal nerve injury. Distal infraorbital nerve chronic constriction injury (dIoN-CCI) evokes pain-related behaviors including increased facial grooming and hyper-responsiveness to acetone (cutaneous cooling) after dIoN-CCI surgery in mice. In addition, dIoN-CCI mice developed conditioned place preference to mirogabalin, suggesting increased neuropathic pain-related aversion. Treatment of the infraorbital nerve with neutralizing antibody HMGB1 (anti-HMGB1 nAb) before dIoN-CCI prevented both facial grooming and hyper-responsiveness to cooling. Pretreatment with anti-HMGB1 nAb also blocked immune cell activation associated with trigeminal nerve injury including the accumulation of macrophage around the injured IoN and increased microglia activation in the ipsilateral spinal trigeminal nucleus caudalis. The current findings demonstrated that blocking of HMGB1 prior to nerve injury prevents the onset of pain-related behaviors, possibly through blocking the activation of immune cells associated with the nerve injury, both within the CNS and on peripheral nerves. The current findings further suggest that blocking HMGB1 before tissue injury could be a novel strategy to prevent the induction of chronic pain following orofacial surgeries.

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