Therapeutic potential of HMGB1-targeting agents in sepsis

Wang, Haichao; Zhu, Shu; Zhou, Rongrong; Li, Wei; Sama, Andrew E.

doi:10.1017/s1462399408000884

Cited by 103 publications

(122 citation statements)

References 162 publications

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“…been thought that extracellular HMGB1 is a late mediator of sepsis (29); however, it is also upregulated by activated platelets in the early phase of sepsis (30). HMGB1 acts as an early and late mediator of septic lethality.…”

Section: Figure 3 Sequential Changes In Blood Sample Values At 6 H mentioning

confidence: 99%

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction

Sakurai

Miyashita

Okazaki

et al. 2017

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Abstract. Background Sepsis is a clinical syndrome of systemic inflammatory responses arising from an infectious process with a presumed or known focus (1, 2). Severe sepsis, defined as sepsis with acute organ dysfunction, is associated with high morbidity and mortality rates (3). Inflammation and coagulation play pivotal roles in the pathogenesis of sepsis (4, 5). Sepsis-induced multiple organ failure (MOF) has numerous causes, such as various types of shock, adult respiratory distress syndrome (ARDS), and disseminated intravascular coagulation (DIC) (6). Gando et al. (7) reported that DIC is frequently associated with systemic inflammatory response syndrome (SIRS; 83%) and that such patients have a high mortality rate (63%). Ogura et al. (4) evaluated coagulation activity, organ dysfunction, and SIRS in critically-ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation. In critically-ill patients with thrombocytopenia, they found that coagulopathy and organ dysfunction progressed with a significant mutual correlation, depending on the increase in SIRS scores. Thus, SIRSassociated coagulopathy may play a critical role in inducing organ dysfunction after severe insult. 1051This article is freely accessible online.Correspondence to: Tomoharu Miyashita,

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Section: Figure 3 Sequential Changes In Blood Sample Values At 6 H mentioning

confidence: 99%

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction

Sakurai

Miyashita

Okazaki

et al. 2017

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“…These HMGBs are structured into three domains-two basic HMG boxes (HMG domains A and B) and a highly acidic C-terminal tail. 3,4 Via these HMG boxes, HMGBs can interact with various proteins ranging from nuclear cellular proteins to viral proteins. Our group proposed a novel role for the HMGB1 protein in the cell growth and radiosensitivity through RB-interaction-dependent and -independent mechanisms.…”

Section: Fig 2 Hmgbs Bind To Rb (A)mentioning

confidence: 99%

“…HMGB1-2 proteins play an important role in gene transcription, DNA recombination and repair, cell replication, and autophagy via interacting with a number of key cellular proteins, including transcriptional factors, site-specific recombination, and DNA repair proteins. [2][3][4][5] Moreover, there is increasing evidence that HMGB1 and HMGB2 are novel prognostic markers and potential therapeutic targets for different types of cancers, including breast carcinoma, hepatocellular carcinoma, and squamous-cell carcinoma. [6][7][8][9][10] Consistently, enforced expression of HMGB1 alters the sensitivity of cancer cells to DNA-damaging agents.…”

Section: Introductionmentioning

confidence: 99%

High-Mobility Group Boxes Mediate Cell Proliferation and Radiosensitivity via Retinoblastoma-Interaction-Dependent and -Independent Mechanisms

Wang

Meng²,

Jiao³

et al. 2012

Cancer Biotherapy and Radiopharmaceuticals

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Our previous studies have shown that high-mobility group box 1 (HMGB1) could physically associate with the retinoblastoma (RB) protein via an LXCXE (leucine-X-cysteine-X-glutamic; X = any amino acid) motif. An identical LXCXE motif is present in the HMGB1-3 protein sequences, whereas a near-consensus LXCXD (leucine-X-cysteine-X-asparagine; X = any amino acid) motif is found in the HMGB4 protein. In this study, we have demonstrated that like HMGB1, HMGB2-3 also associated with the RB in vitro and in vivo, as evidenced by glutathione-s-transferase capture and immunoprecipitation-Western blot assays. A point mutation of the LXCXE or LXCXD motif led to disruption of RB:HMGB1-4 interactions. Enforced expression of HMGB1-3 or HMGB4 by adenoviral-vector-mediated gene transfer resulted in significant inhibition of breast cancer cell proliferation through an LXCXE-or LXCXD-dependent mechanism and an increased radiosensitivity through an LXCXE-or LXCXD-independent mechanism. These results suggest an important role of the LXCXE/D motif in RB:HMGB1-4 association and modulation of cancer cell growth, but not radiosensitivity.

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“…The amount of HMGB-1 is significantly correlated with the disseminated intravascular coagulation (DIC) score and the sepsis-related organ failure assessment (SOFA) score 6 . HMGB-1 is a 30 kDa indispensable protein, which was discovered as a DNA binding protein and is a mediator of cell death when it circulates through the body 7 . It has also been identified as one of the lethal mediators at the late stage of sepsis There are treatment guidelines for sepsis and septic shock, such as the surviving sepsis campaign guidelines (SSCG) 13 and the Japanese guidelines for the management of sepsis 14 .…”

Section: Introductionmentioning

confidence: 99%

Plasma Adsorption Membranes Are Able to Efficiently Remove High Mobility Group Box-1 (HMGB-1)

2018

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Background: High Mobility Group Box 1 (HMGB-1) is a 30 kDa protein that is a lethal mediator in sepsis and is a recognized therapeutic target. However, no consensus has been reached for acute blood purification therapy as a treatment for sepsis targeting HMGB-1. Previous studies demonstrated that a high anti-HMGB-1 antibody titer and the suppression of HMGB-1 activity improved survival rate in animal sepsis models. The aim of this study was to evaluate whether plasma adsorption therapy is able to decrease the level of HMGB-1, representing a new potential treatment strategy against sepsis.Methods: Plasma adsorption therapy has been known as a treatment for various autoimmune diseases.Three different adsorbent columns, including TR-350 (IM-TR), PH-350 (IM-PH), and BRS-350 (BRS), were used in this study for comparison.We made a 1/350 scale of these three columns. Fetal bovine serum (FBS) contains a significant amount of HMGB-1. After priming with saline, FBS was passed through the columns and the adsorption rates of HMGB-1 at 25 minutes, 50 minutes, and 75 minutes were evaluated. The total adsorbed HMGB-1 level at 75 minutes was also calculated. Results:The highest adsorption rate and total adsorbed amount of HMGB-1 were observed in IM-TR, followed by BRS and IM-PH. IM-TR showed a decline in adsorption rate over time. BRS showed a steady adsorption rate at all time points. IM-TR removed HMGB-1 significantly more than IM-PH and BRS.Conclusions: Our findings showed that plasma adsorption therapy efficiently adsorbed HMGB-1 and could be safely applied for the treatment of sepsis. (J Nippon Med Sch 2018; 85: 150 156)

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Therapeutic potential of HMGB1-targeting agents in sepsis

Cited by 103 publications

References 162 publications

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction

High-Mobility Group Boxes Mediate Cell Proliferation and Radiosensitivity via Retinoblastoma-Interaction-Dependent and -Independent Mechanisms

Plasma Adsorption Membranes Are Able to Efficiently Remove High Mobility Group Box-1 (HMGB-1)

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