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.

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.

The Role of High Mobility Group Box 1 (HMGB1) in Neurodegeneration: A Systematic Review

2022 ◽  
Vol 20 ◽  
Author(s):  
Fathimath Zaha Ikram ◽  
Alina Arulsamy ◽  
Thaarvena Retinasamy ◽  
Mohd. Farooq Shaikh
Keyword(s):  
Systematic Review ◽  
Tissue Injury ◽  
High Mobility ◽  
High Mobility Group ◽  
Hmgb1 Protein ◽  
Toll Like Receptor 4 ◽  
Neuroinflammatory Response ◽  
Molecular Pattern ◽  
Glycation End Products

Background: High mobility group box 1 (HMGB1) protein is a damage-associated molecular pattern (DAMP) molecule that plays an important role in the repair and regeneration of tissue injury. It also acts as a pro-inflammatory cytokine through the activation of toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), to elicit the neuroinflammatory response. HMGB1 may aggravate several cellular responses which may lead to pathological inflammation and cellular death. Thus, there have been a considerable amount of research into the pathological role of HMGB1 in diseases. However, whether the mechanism of action of HMGB1 is similar in all neurodegenerative disease pathology remains to be determined. Objective: Therefore, this systematic review aimed to critically evaluate and elucidate the role of HMGB1 in the pathology of neurodegeneration based on the available literature. Methods: A comprehensive literature search was performed on four databases; EMBASE, PubMed, Scopus, and CINAHL Plus. Results: A total of 85 articles were selected for critical appraisal, after subjecting to the inclusion and exclusion criteria in this study. The selected articles revealed that HMGB1 levels were found elevated in most neurodegeneration except in Huntington’s disease and Spinocerebellar ataxia, where the levels were found decreased. This review also showcased that HMGB1 may act on distinctive pathways to elicit its pathological response leading to the various neurodegeneration processes/diseases. Conclusion: While there have been promising findings in HMGB1 intervention research, further studies may still be required before any HMGB1 intervention may be recommended as a therapeutic target for neurodegenerative diseases.

scholarly journals Innate Immunity Effector Cells as Inflammatory Drivers of Cardiac Fibrosis

2020 ◽  
Vol 21 (19) ◽  
pp. 7165 ◽  
Author(s):  
Denisa Baci ◽  
Annalisa Bosi ◽  
Luca Parisi ◽  
Giuseppe Buono ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Cells ◽  
Cardiac Fibrosis ◽  
Immune Cell ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Sterile Inflammation ◽  
Therapeutic Interventions ◽  
Ecm Remodeling

Despite relevant advances made in therapies for cardiovascular diseases (CVDs), they still represent the first cause of death worldwide. Cardiac fibrosis and excessive extracellular matrix (ECM) remodeling are common end-organ features in diseased hearts, leading to tissue stiffness, impaired myocardial functional, and progression to heart failure. Although fibrosis has been largely recognized to accompany and complicate various CVDs, events and mechanisms driving and governing fibrosis are still not entirely elucidated, and clinical interventions targeting cardiac fibrosis are not yet available. Immune cell types, both from innate and adaptive immunity, are involved not just in the classical response to pathogens, but they take an active part in “sterile” inflammation, in response to ischemia and other forms of injury. In this context, different cell types infiltrate the injured heart and release distinct pro-inflammatory cytokines that initiate the fibrotic response by triggering myofibroblast activation. The complex interplay between immune cells, fibroblasts, and other non-immune/host-derived cells is now considered as the major driving force of cardiac fibrosis. Here, we review and discuss the contribution of inflammatory cells of innate immunity, including neutrophils, macrophages, natural killer cells, eosinophils and mast cells, in modulating the myocardial microenvironment, by orchestrating the fibrogenic process in response to tissue injury. A better understanding of the time frame, sequences of events during immune cells infiltration, and their action in the injured inflammatory heart environment, may provide a rationale to design new and more efficacious therapeutic interventions to reduce cardiac fibrosis.

scholarly journals GABAA receptor α4-subunit knockout enhances lung inflammation and airway reactivity in a murine asthma model

2017 ◽  
Vol 313 (2) ◽  
pp. L406-L415 ◽  
Author(s):  
Gene T. Yocum ◽  
Damian L. Turner ◽  
Jennifer Danielsson ◽  
Matthew B. Barajas ◽  
Yi Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Immune Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Asthma Model

Emerging evidence indicates that hypnotic anesthetics affect immune function. Many anesthetics potentiate γ-aminobutyric acid A receptor (GABAAR) activation, and these receptors are expressed on multiple subtypes of immune cells, providing a potential mechanistic link. Like immune cells, airway smooth muscle (ASM) cells also express GABAARs, particularly isoforms containing α4-subunits, and activation of these receptors leads to ASM relaxation. We sought to determine if GABAAR signaling modulates the ASM contractile and inflammatory phenotype of a murine allergic asthma model utilizing GABAAR α4-subunit global knockout (KO; Gabra40/0) mice. Wild-type (WT) and Gabra4 KO mice were sensitized with house dust mite (HDM) antigen or exposed to PBS intranasally 5 days/wk for 3 wk. Ex vivo tracheal rings from HDM-sensitized WT and Gabra4 KO mice exhibited similar magnitudes of acetylcholine-induced contractile force and isoproterenol-induced relaxation ( P = not significant; n = 4). In contrast, in vivo airway resistance (flexiVent) was significantly increased in Gabra4 KO mice ( P < 0.05, n = 8). Moreover, the Gabra4 KO mice demonstrated increased eosinophilic lung infiltration ( P < 0.05; n = 4) and increased markers of lung T-cell activation/memory (CD62L low, CD44 high; P < 0.01, n = 4). In vitro, Gabra4 KO CD4+ cells produced increased cytokines and exhibited increased proliferation after stimulation of the T-cell receptor as compared with WT CD4+ cells. These data suggest that the GABAAR α4-subunit plays a role in immune cell function during allergic lung sensitization. Thus GABAAR α4-subunit-specific agonists have the therapeutic potential to treat asthma via two mechanisms: direct ASM relaxation and inhibition of airway inflammation.

scholarly journals Immunomodulation of Epithelium

1996 ◽  
Vol 10 (4) ◽  
pp. 243-248 ◽  
Author(s):  
Mary H Perdue
Keyword(s):  
Mast Cell ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Regulatory System ◽  
Mast Cell Activation ◽  
Immune Cell Activation ◽  
Inflammatory Conditions ◽  
Close Proximity ◽  
Antigenic Material

Many studies have provided evidence that the immune system is a key regulatory system of intestinal function. The interaction of immune cells with the gut epithelium plays an important role in host defence, acting to eliminate pathogens, antigens and other noxious material from the lumen of the gastrointestinal tract. During inflammatory conditions of the gut, the mucosa becomes packed with immune cells in close proximity to the enterocytes. Mediators released from these cells have profound effects on epithelial functions. The two main functions of the intestinal epithelium are to transport nutrients, ions and water, and to act as a barrier to prevent unimpeded uptake of antigenic material and microbes from the lumen. Both these functions are altered by immune reactions in response to various stimuli. Topics discussed include mast cells and epithelial function; mast cell-nerve interaction; mast cell activation; neutrophils, eosinophils and macrophages; T cells; and prostaglandins and immune cell activation.

Integrative immunophysiology in the intestinal mucosa

1994 ◽  
Vol 267 (2) ◽  
pp. G151-G165 ◽  
Author(s):  
M. H. Perdue ◽  
D. M. McKay
Keyword(s):  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Intestinal Epithelial ◽  
Immune Cell Activation ◽  
Current State ◽  
Enteric Nerves ◽  
Host Defense Response ◽  
Acid Metabolites ◽  
Epithelial Physiology

Over the past ten years, it has become evident that intestinal epithelial functions such as ion secretion are a host defense response to the presence of antigens, microbes, and other noxious substances in the gut lumen. Such responses are mediated by the activation of immune cells in the mucosa causing release of chemical mediators that act directly or indirectly on the epithelium. Frequently, immune cell products stimulate enteric nerves resulting in amplification. Thus immune cells and nerves form interactive units that can recognize various stimuli both specifically and nonspecifically and initiate mechanisms to eliminate offending material. Here, we review the current state of knowledge regarding immune regulation of epithelial physiology with particular emphasis on the ability of immune cells and their products (biogenic amines, cytokines, arachidonic acid metabolites, oxidants) to alter electrolyte transport. The mast cell will be highlighted in this scheme as this cell has been, and continues to be, the focus of extensive research efforts. However, recently it has become apparent that cells such as lymphocytes, macrophages, and polymorphonuclear leukocytes also play important roles in immunophysiology. The effect of immune cell activation on epithelial functions other than transport, such as permeability, proliferation, and antigen presentation, will be described where appropriate. Finally, we will present evidence that the enterocyte can express an "activated" phenotype and thus participate directly in mucosal immune responses.

scholarly journals Leukocyte-derived High-mobility group box 1 controls innate immune responses against Listeria monocytogenes

2019 ◽  
Author(s):  
Annika Volmari ◽  
Katharina Foelsch ◽  
Karsten Yan ◽  
Minyue Qi ◽  
Karlotta Bartels ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Immune Responses ◽  
Tissue Injury ◽  
Myeloid Cells ◽  
High Mobility ◽  
Severe Infection ◽  
High Mobility Group ◽  
Inflammatory Monocyte ◽  
Bacterial Dissemination ◽  
Monocyte Recruitment

AbstractHigh-mobility group box 1 (HMGB1) is a damage-associated molecular pattern with key proinflammatory functions following tissue injury. Moreover, HMGB1 neutralization was shown to alleviate LPS-induced shock, suggesting a role for the protein as a master therapeutic target for inflammatory and infectious diseases. Here, we report that HMGB1 neutralization impedes immune responses to Listeria monocytogenes, a wide-spread bacterium with pathogenic relevance for humans and rodents. Using genetic deletion strategies and neutralizing antibodies, we demonstrate that hepatocyte HMGB1, a major driver of post-necrotic inflammation in the liver, is dispensable for pathogen defense during moderately severe infection with listeria. In contrast, antibody-mediated HMGB1 neutralization and HMGB1 deficiency in myeloid cells effectuate rapid and uncontrolled bacterial dissemination in mice despite preserved basic leukocyte functionality and autophagy induction. During overwhelming infection, hepatocyte injury may contribute to increased HMGB1 serum levels and excessive inflammation in the liver, supporting context-dependent roles for HMGB1 from different cellular compartments during infection. We provide mechanistic evidence that HMGB1 from circulating immune cells contributes to the timely induction of hepatic immune regulatory gene networks, early inflammatory monocyte recruitment to the liver and promotion of neutrophil survival, which are mandatory for pathogen control. In summary, our data establish HMGB1 as a critical co-factor in the immunological clearance of listeria, and argue against HMGB1 neutralization as a universal therapeutic strategy for sepsis.Author summaryHigh-mobility group box 1 (HMGB1) is an abundantly expressed nucleoprotein with signaling properties following secretion or release into the extracellular space. Given its central immune-regulatory roles during tissue injury and LPS-induced septic shock, interventions aimed at HMGB1 signaling have been advocated as therapeutic options for various disease conditions. Here, we show that antibody-mediated HMGB1 neutralization interferes with immunological defense against Listeria monocytogenes, a gram-positive bacterium with high pathogenic relevance for rodents and humans, effectuating uncontrolled bacterial growth and inflammation. Using conditional knockout animals, we demonstrate that while leukocyte functionality is preserved in HMGB1-deficient myeloid cells, HMGB1 released in response to Listeria triggers hepatic inflammatory monocyte recruitment and activation of transcriptional immune networks required for the early control of bacterial dissemination. Hepatocyte HMGB1, a key driver of post-necrotic inflammation in the liver, is dispensable for the immune response during moderately severe infection, but likely contributes to excessive hepatitis when infection is uncontrolled and cellular injury is high. We demonstrate a critical and non-redundant role for HMGB1 in the immune-mediated clearance of listeriosis and argue against HMGB1 neutralization as a universal therapeutic option in the context of infection.

scholarly journals Interactions between tumor-derived proteins and Toll-like receptors

2020 ◽  
Vol 52 (12) ◽  
pp. 1926-1935
Author(s):  
Gun-Young Jang ◽  
Ji won Lee ◽  
Young Seob Kim ◽  
Sung Eun Lee ◽  
Hee Dong Han ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
T Cell Activation ◽  
Immune Cells ◽  
Cell Activation ◽  
Tissue Injury ◽  
Suppressor Cells ◽  
Toll Like Receptors ◽  
Molecular Pattern ◽  
Molecular Patterns ◽  
Dying Cells

AbstractDamage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment.

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