scholarly journals High Mobility Group 1 Protein (Hmg-1) Stimulates Proinflammatory Cytokine Synthesis in Human Monocytes

2000 ◽  
Vol 192 (4) ◽  
pp. 565-570 ◽  
Author(s):  
Ulf Andersson ◽  
Haichao Wang ◽  
Karin Palmblad ◽  
Ann-Charlotte Aveberger ◽  
Ona Bloom ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Tissue Injury ◽  
Human Peripheral Blood ◽  
Passive Immunization ◽  
High Mobility ◽  
High Mobility Group ◽  
Computer Assisted ◽  
Cytokine Release ◽  
Cytokine Synthesis ◽  
Group 1

Lipopolysaccharide (LPS) is lethal to animals because it activates cytokine release, causing septic shock and tissue injury. Early proinflammatory cytokines (e.g., tumor necrosis factor [TNF] and interleukin [IL]-1) released within the first few hours of endotoxemia stimulate mediator cascades that persist for days and can lead to death. High mobility group 1 protein (HMG-1), a ubiquitous DNA-binding protein, was recently identified as a “late” mediator of endotoxin lethality. Anti–HMG-1 antibodies neutralized the delayed increase in serum HMG-1, and protected against endotoxin lethality, even when passive immunization was delayed until after the early cytokine response. Here we examined whether HMG-1 might stimulate cytokine synthesis in human peripheral blood mononuclear cell cultures. Addition of purified recombinant HMG-1 to human monocyte cultures significantly stimulated the release of TNF, IL-1α, IL-1β, IL-1RA, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and MIP-1β; but not IL-10 or IL-12. HMG-1 concentrations that activated monocytes were within the pathological range previously observed in endotoxemic animals, and in serum obtained from septic patients. HMG-1 failed to stimulate cytokine release in lymphocytes, indicating that cellular stimulation was specific. Cytokine release after HMG-1 stimulation was delayed and biphasic compared with LPS stimulation. Computer-assisted image analysis demonstrated that peak intensity of HMG-1–induced cellular TNF staining was comparable to that observed after maximal stimulation with LPS. Administration of HMG-1 to Balb/c mice significantly increased serum TNF levels in vivo. Together, these results indicate that, like other cytokine mediators of endotoxin lethality (e.g., TNF and IL-1), extracellular HMG-1 is a regulator of monocyte proinflammatory cytokine synthesis.

scholarly journals Variability in Arabidopsis Thaliana Chromosomal High-Mobility-Group-1-Like Proteins

1997 ◽  
Vol 250 (3) ◽  
pp. 646-652 ◽  
Author(s):  
Christian Stemmer ◽  
Christoph Ritt ◽  
Gabor L. Igloi ◽  
Rudi Grimm ◽  
Klaus D. Crasser
Keyword(s):  
Arabidopsis Thaliana ◽  
High Mobility ◽  
High Mobility Group ◽  
Group 1

scholarly journals Phosphorylation of high mobility group 1 protein by phospholipid-sensitive Ca2+-dependent protein kinase from pig testis

1985 ◽  
Vol 227 (1) ◽  
pp. 271-276 ◽  
Author(s):  
K Kimura ◽  
N Katoh ◽  
K Sakurada ◽  
S Kubo
Keyword(s):  
Protein Kinase ◽  
High Mobility ◽  
Particulate Fraction ◽  
High Mobility Group ◽  
Hmg Proteins ◽  
Dependent Protein Kinase ◽  
Histone Proteins ◽  
Km Value ◽  
Dependent Protein ◽  
Group 1

Phospholipid-sensitive Ca2+-dependent protein kinase was partially purified from total particulate fraction of pig testis. The enzyme phosphorylated high mobility group 1 protein (HMG 1), one of the major chromatin-associated non-histone proteins. Other HMG proteins (HMG 2, 14 and 17) were not phosphorylated by the enzyme. Exhaustive phosphorylation of HMG 1 revealed that 1 mol of phosphate was incorporated/mol of HMG 1. The apparent Km value for HMG 1 was 3.66 microM. 1,3-Diolein stimulated the phosphorylation at 10 microM-Ca2+ in the presence of phosphatidylserine. The phosphorylation of HMG 1 was inhibited by adriamycin, an inhibitor of spermatogenesis.

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 The Proinflammatory Cytokine High-Mobility Group Box-1 Mediates Retinal Neuropathy Induced by Diabetes

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ahmed M. Abu El-Asrar ◽  
Mohammad Mairaj Siddiquei ◽  
Mohd Imtiaz Nawaz ◽  
Karel Geboes ◽  
Ghulam Mohammad
Keyword(s):  
Tyrosine Hydroxylase ◽  
Proinflammatory Cytokine ◽  
Caspase 3 ◽  
High Mobility ◽  
Diabetic Rats ◽  
High Mobility Group ◽  
Hmgb1 Protein ◽  
Epiretinal Membranes ◽  
Glyoxalase 1 ◽  
Extracellular Signal

To test the hypothesis that increased expression of proinflammatory cytokine high-mobility group box-1 (HMGB1) in epiretinal membranes and vitreous fluid from patients with proliferative diabetic retinopathy and in retinas of diabetic rats plays a pathogenetic role in mediating diabetes-induced retinal neuropathy. Retinas of 1-month diabetic rats and HMGB1 intravitreally injected normal rats were studied using Western blot analysis, RT-PCR and glutamate assay. In addition, we studied the effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced biochemical changes in the retina. Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of HMGB1 protein and mRNA, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2), cleaved caspase-3 and glutamate; and significant downregulation of synaptophysin, tyrosine hydroxylase, glutamine synthetase, and glyoxalase 1. Constant glycyrrhizin intake from the onset of diabetes did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of HMGB1 protein and mRNA, activated ERK1/2, cleaved caspase-3, and glutamate. In the glycyrrhizin-fed diabetic rats, the decrease in synaptophysin, tyrosine hydroxylase, and glyoxalase 1 caused by diabetes was significantly attenuated. These findings suggest that early retinal neuropathy of diabetes involves upregulated expression of HMGB1 and can be ameliorated by inhibition of HMGB1.

Inhibition of poly(ADP-ribose) polymerase attenuates inflammation in a model of chronic colitis

2000 ◽  
Vol 279 (3) ◽  
pp. G641-G651 ◽  
Author(s):  
Humberto B Jijon ◽  
Thomas Churchill ◽  
David Malfair ◽  
Andreas Wessler ◽  
Laurence D Jewell ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Proinflammatory Cytokine ◽  
Time Course ◽  
Nitrosative Stress ◽  
Tissue Injury ◽  
Parp Inhibitor ◽  
Interferon Γ ◽  
Cytokine Release ◽  
Energy Status ◽  
Deficient Mice

Crohn's disease is a chronic disease characterized by oxidant-induced tissue injury and increased intestinal permeability. A consequence of oxidative damage is the accumulation of DNA strand breaks and activation of poly(ADP-ribose) polymerase (PARP), which subsequently catalyzes ADP-ribosylation of target proteins. In this study, we assessed the role of PARP in the colitis seen in interleukin (IL)-10 gene-deficient mice. IL-10 gene-deficient mice demonstrated significant alterations in colonic cellular energy status in conjunction with increased permeability, proinflammatory cytokine release, and nitrosative stress. After 14 days of treatment with the PARP inhibitor 3-aminobenzamide, IL-10 gene-deficient mice demonstrated normalized colonic permeability; reduced tumor necrosis factor-α and interferon-γ secretion, inducible nitric oxide synthase expression, and nitrotyrosine levels; and significantly attenuated inflammation. Time course studies demonstrated that 3-aminobenzamide rapidly altered cellular metabolic activity and decreased cellular lactate levels. This was associated with normalization of colonic permeability and followed by a downregulation of proinflammatory cytokine release. Our data demonstrate that inhibition of PARP activity results in a marked improvement of colonic inflammatory disease and a normalization of cellular metabolic function and intestinal permeability.

scholarly journals Characterization of a High Mobility Group 1/2 Homolog in Yeast

1996 ◽  
Vol 271 (52) ◽  
pp. 33678-33685 ◽  
Author(s):  
Jian Lu ◽  
Ryuji Kobayashi ◽  
Steven J. Brill
Keyword(s):  
High Mobility ◽  
High Mobility Group ◽  
Group 1

Stimulated astrocytes release high-mobility group 1 protein, an inducer of LAN-5 neuroblastoma cell differentiation

Neuroscience ◽  
1997 ◽  
Vol 82 (4) ◽  
pp. 1021-1028 ◽  
Author(s):  
M Passalacqua ◽  
M Patrone ◽  
G.B Picotti ◽  
M Del Rio ◽  
B Sparatore ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Neuroblastoma Cell ◽  
High Mobility ◽  
High Mobility Group ◽  
Group 1

Does high mobility group 1 protein function as a late mediator for LPS- or TNF-induced shock in galactosamine-sensitized mice?

2002 ◽  
Vol 8 (5) ◽  
pp. 391-398 ◽  
Author(s):  
Ryoichi Hasunuma ◽  
Hiroko Maruyama ◽  
Hiroaki Takimoto ◽  
Roland Ryll ◽  
Shigenori Tanaka ◽  
...  
Keyword(s):  
Protein Function ◽  
High Mobility ◽  
High Mobility Group ◽  
Group 1

Uric Acid Induces High Mobility Group Box1 Protein Release in Monocytes/Macrophages through P38 MAPK, ERK1/2, JNK and AP-1 Activation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1464-1464
Author(s):  
Kamal K. Biswas ◽  
Yoko Oyama ◽  
Kazuhiro Abeyama ◽  
Teruto Hashiguchi ◽  
Ikuro Maruyama
Keyword(s):  
Cell Death ◽  
Uric Acid ◽  
Renal Disease ◽  
P38 Mapk ◽  
Proinflammatory Cytokine ◽  
High Mobility ◽  
High Mobility Group ◽  
Mitogen Activated Protein Kinase ◽  
Trypan Blue Exclusion ◽  
Cell Death Pathway

Abstract Uric acid, a final metabolite of purine metabolism has gained attention for its pathogenic role in the development of hypertension, vascular disease, renal disease, and cardiovascular events. Recent studies have shown that soluble uric acid induces proliferation as well as synthesis of proinflammatory chemokine, monocyte chemoattractant protein 1 in rat vascular smooth muscle cells. It also stimulates human monolayer cells to produce IL-1B. IL-6 and TNF alpha. However, high mobility group box 1(HMGB1), a non histone DNA binding protein which is recently identified as a proinflammatory cytokine and can be released from cells of the macrophage/monocyte lineage by proinflammatory stimuli or by cells undergoing necrotic cell death pathway. In the present study, we hypothesized that soluble uric acid may stimulates monocytes/macrophages to release HMGB1. Here we demonstrate that crystal and endotoxin free uric acid triggers the release of HMGB1 in a time and dose dependant fashion in mouse macrophage cells, Raw 264.7, human leukemic promonocytes(THP-1 cells) as well as in macrophages but not in fibroblast obtained from synovial fluid of rheumatoid arthritis patients. Moreover, translocation of HMGB1 to the cytoplasm before secreted in the extracellular milieu was significantly detected within 6h of Uric acid exposure. No loss of cell viability was observed in our experimental condition as judged by trypan blue exclusion, MTT reduction and LDH release assays, indicating that HMGB1 release was not due to cell death. Uric acid treatment resulted in the activation of p38 mitogen activated protein kinase(MAPK), c-Jun N terminal kinase(JNK) and extracellular regulatroy kinase (ERK1/2). Inhibition of each of p38 MAPK, ERK1/2 and JNK by using potent and selective inhibitors, SB203580, U0126 and SP60012 respectively, almost completely blocked uric acid-induced HMGB1 release. Furthermore, Curcumin, a potent inhibitor of the transcription factor, activator protein 1(AP-1) strongly suppressed HMGB1 release, indicating that these signaling patways are essential for the induction of HMGB1 release in response to uric acid. In conclusion, our data suggest that uric acid may regulate critical proinflammatory pathways at least in part through its action as a monocyte/macrophage derived potent proinflammatory cytokine, HMGB1 release. This may play pathologic role for hyperuricemia-induced morbidities including arthritis, atherosclerosis, renal disease and so on.

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