Sterile Inflammatory Role of High Mobility Group Box 1 Protein: Biological Functions and Involvement in Disease

Gonelevue, Sera; Bandyopadhyay, Abhirup; Bhagat, Sanjeev; Alam, Iqbal; Khan, Gausal A.

doi:10.1159/000491390

Cited by 8 publications

(19 citation statements)

References 114 publications

(150 reference statements)

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“…High mobility group box-1 protein, a non-histone DNA binding protein, can activate multiple inflammatory pathways, including NFκB, extracellular regulated kinase, p38, CD24, Tolllike receptor-2, Toll-like receptor-4, Toll-like receptor-9, and the advanced glycation end-product receptor [84]. EPA has been shown to reduce high mobility group box-1 protein and TNFα by a PPARγ-dependent mechanism, and by a PPARγ-independent pathway inhibiting the glycation end-product and TLR9, which has shown to attenuate ischemic brain damage in ovariectomized rats [85].…”

Section: Inflammationmentioning

confidence: 99%

EPA’s pleiotropic mechanisms of action: a narrative review

Nelson¹,

Budoff²,

Wani

et al. 2021

Postgraduate Medicine

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Treatment with icosapent ethyl 4 g/day, a highly purified and stable ethyl ester of eicosapentaenoic acid (EPA), demonstrated a significant reduction in atherosclerotic cardiovascular disease (ASCVD) events and death in REDUCE-IT. However, analyses of REDUCE-IT and meta-analyses have suggested that this clinical benefit is greater than can be achieved by triglyceride reduction alone. EPA therefore may have additional pleiotropic effects, including anti-inflammatory and anti-aggregatory mechanisms. EPA competes with arachidonic acid for cyclooxygenase and lipoxygenase, producing anti-inflammatory and anti-aggregatory metabolites rather than the more deleterious metabolites associated with arachidonic acid. Changing the EPA:arachidonic acid ratio may shift metabolic status from pro-inflammatory/pro-aggregatory to anti-inflammatory/anti-aggregatory. EPA also has antioxidant effects and increases synthesis of nitric oxide. Incorporation of EPA into phospholipid bilayers influences membrane structure and may help to prevent cardiac arrhythmias. Clinically, this may translate into improved vascular health, including regression of atherosclerotic plaque. Overall, EPA has a range of pleiotropic effects that contribute to a reduction in ASCVD.

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Section: Inflammationmentioning

confidence: 99%

EPA’s pleiotropic mechanisms of action: a narrative review

Nelson¹,

Budoff²,

Wani

et al. 2021

Postgraduate Medicine

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“…High-mobility group box 1 (HMGB1) is a highly conserved non-histone DNA-binding protein ( 9 ). It has been documented that HMGB, an extracellularly released mediator, can regulate the inflammatory response ( 10 ). Typically, the production of pro-inflammatory cytokines such as TNF-α and IL-1β is induced immediately once inflammation spreads into the blood stream, which then triggers HMGB1 expression ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

“…Existing evidence indicates that extracellular HMGB1 may exhibit pro-inflammatory activity in the pathogenesis of various inflammatory diseases ( 12 ). HMGB1 is secreted by injured cells and innate immune cells including macrophages ( 10 , 13 ). Moreover, in response to LPS stimulation, HMGB1 can translocate from the nuclei to the cytoplasm in macrophages ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑23a‑3p targeting of HMGB1 inhibits LPS‑induced inflammation in murine macrophages in vitro

Sun

Wang

2022

Exp Ther Med

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Inflammatory cytokines, including high mobility group box 1 (HMGB1), play a key role in sepsis via various mechanisms, some of which remain unknown. Sepsis is a common cause of death in patients admitted to the intensive care unit. MicroRNAs (miRs) serve an important role in the inflammatory response. The present study aimed to investigate the role of miR-23a-3p in macrophage inflammation and the targeted regulation of HMGB1 expression. The murine macrophage cell line RAW264.7 was subjected to lipopolysaccharide (LPS) treatment to mimic the inflammation involved in sepsis in vitro. Reverse transcription-quantitative PCR was performed to measure miR-23a-3p expression and mRNA expression. Protein levels were determined using ELISA and western blotting. The target binding relationship between miR-23a-3p and the HMGB1 3'untranslated region was predicted and validated with a dual luciferase reporter assay. HMGB1 expression was increased and miR-23a-3p expression significantly reduced in patients with sepsis and in LPS-treated RAW264.7 cells in comparison with controls. Overexpression of miR-23a-3p reduced interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression in RAW264.7 cells under LPS stimulation, while silencing of miR-23a-3p elevated the expression of IL-6 and TNF-α in comparison with controls. The inhibitory effect of miR-23a-3p on LPS-induced inflammation could be abolished by HMGB1 upregulation in RAW264.7 cells. HMGB1 was targeted by miR-23a-3p. miR-23a-3p is expressed at reduced levels during inflammation in sepsis, and overexpression of miR-23a-3p inhibits LPS-induced inflammation in murine macrophages in vitro by directly downregulating HMGB1. The results of the present study provided a novel insight into the molecular mechanism underlying HMGB1 expression at the post-transcriptional level in sepsis.

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“…The interaction of HMGB1 with transmembrane receptors such as Toll-like receptors (TLR)-2, TLR-4, TLR-9, and the receptor for advanced glycation end-products (RAGE) activated pro-inflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and IL-8. As a result, a sterile inflammatory response to tissue damage occurs 18 , 19 .…”

Section: Introductionmentioning

confidence: 99%

Second-trimester serum high mobility group box-1 and uterine artery Doppler to predict preeclampsia

Wairachpanich

Phupong

2022

Sci Rep

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The objective of this study was to identify the predictive value for preeclampsia of second-trimester serum high mobility group box-1 (HMGB1) and uterine artery Doppler in singleton pregnancies. Between April 2020 and April 2021, a prospective study was conducted on singleton pregnancies with a gestational age of 16–20+6 weeks at King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Maternal characteristics, uterine artery Doppler, and serum HMGB1 were collected. Serum HMGB1 levels and mean uterine artery pulsatility index (UAPI) were combined to calculate the predictive value for preeclampsia. A total of 393 pregnant women were analyzed, with 25 cases (6.4%) developing preeclampsia and 5 cases (1.3%) developing early-onset preeclampsia. Baseline characteristics of preeclampsia and normal pregnant women were comparable. Preeclamptic pregnant women had significantly higher mean serum HMGB1 levels than normal pregnant women (1112.8 ± 363.1 ng/mL vs 910.8 ± 486.1 ng/mL, p = 0.013). There was no difference in the mean UAPI. Any early-diastolic notching was found more frequently in the preeclampsia group (32.0% vs 12.5%, p = 0.013). The cut-off value for serum HMGB1 levels above 1.04 MoM as abnormal value to predict preeclampsia had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 88.0%, 53.5%, 11.4% and 98.5%, respectively. When using abnormal serum HMGB1 levels combined with mean UAPI above 95th percentile, the sensitivity, specificity, PPV and NPV to predict preeclampsia were 88.0%, 50.8%, 10.8% and 98.4%, respectively. This study showed that serum HMGB1 at 16–20+6 weeks of gestation were effective in predicting preeclampsia. The addition of UAPI did not improve the prediction performance.

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Sterile Inflammatory Role of High Mobility Group Box 1 Protein: Biological Functions and Involvement in Disease

Cited by 8 publications

References 114 publications

EPA’s pleiotropic mechanisms of action: a narrative review

EPA’s pleiotropic mechanisms of action: a narrative review

MicroRNA‑23a‑3p targeting of HMGB1 inhibits LPS‑induced inflammation in murine macrophages in vitro

Second-trimester serum high mobility group box-1 and uterine artery Doppler to predict preeclampsia

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