Serum Levels of HMGB1 in Postmenopausal Patients with Rheumatoid Arthritis: Associations with Proinflammatory Cytokines, Acute-phase Reactants, and Clinical Disease Characteristics

Pullerits, Rille; Urbonaviciute, Vilma; Voll, Reinhard; Forsblad-d’Elia, Helena; Carlsten, Hans

doi:10.3899/jrheum.110091

Cited by 24 publications

(18 citation statements)

References 10 publications

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“…The expression of HMGB1 is increased at the site of joint inflammation, including the synovial tissue and synovial fluid (Hamada et al, 2008; Kokkola et al, 2002; Taniguchi et al, 2003). Serum HMGB1 level is increased in patients with rheumatoid arthritis (Pullerits et al, 2011). Importantly, injection of HMGB1 into a normal joint caused NF-κB activation, IL-1β production, and the development of arthritis in 80% of animals in one study (Garcia-Arnandis et al, 2010b; Pullerits et al, 2003).…”

Section: Hmgb1 and Diseasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

823

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Section: Hmgb1 and Diseasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

823

828

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“…Moreover, changes in their levels positively correlate with disease severity, progression, and prognosis. Of note, the average level of HMGB1, histone, and DNA in the circulation of these patients is usually measured in nanograms per milliliter (ng/mL) [12,13] whereas the quantities used in in vitro experimental studies usually measures in micrograms per milliliter [ug/mL]) [14,15,16]. This is thus significantly higher than the concentrations found clinically.…”

Section: Introductionmentioning

confidence: 99%

Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

Chen

Lotze

et al. 2015

Biochemical and Biophysical Research Communications

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High mobility group box 1 (HMGB1), histone, and DNA are essential nuclear components involved in the regulation of chromosome structure and function. In addition to their nuclear function, these molecules act as damage-associated molecular patterns (DAMPs) alone or together when released extracellularly. The synergistic effect of these nuclear DNA-HMGB1-histone complexes as DAMP complexes (nDCs) on immune cells remains largely unexplored. Here, we demonstrate that nDCs limit survival of macrophages (e.g., RAW264.7 and peritoneal macrophages) but not cancer cells (e.g., HCT116, HepG2 and Hepa1-6). nDCs promote production of inflammatory tumor necrosis factor α (TNFα) release, triggering reactive oxygen species-dependent apoptosis and necrosis. Moreover, the receptor for advanced glycation end products (RAGE), but not toll-like receptor (TLR)-4 and TLR-2, was required for Akt-dependent TNFα release and subsequent cell death following treatment with nDCs. Genetic depletion of RAGE by RNAi, antioxidant N-Acetyl-L-cysteine, and TNFα neutralizing antibody significantly attenuated nDC-induced cell death. These findings provide evidence supporting novel signaling mechanisms linking nDCs and inflammation in macrophage cell death.

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“…The presence of cytoplasmic and extracellular HMGB1 has been reported in experimental arthritis models as well as in rheumatoid arthritis (RA) in humans. HMGB1 has been detected in the majority of investigated synovial fluid samples from patients with RA [5]. In muscle biopsies from patients with chronic myositis, HMGB1 is detected cytoplasmically in muscle fibers, in inflammatory infiltrates, and in small vessel endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…When released by activated monocytes, HMBG1 activates the release of downstream cytokines that lead to cell death. Further, like other cytokine mediators of endotoxemia, HMGB1 activates human monocytes to release pro-inflammatory cytokines [5]. Therefore, it plays an important role in the pathogenesis of both acute and chronic inflammatory conditions.…”

Section: Introductionmentioning

confidence: 99%

The role of high mobility group box chromosomal protein 1 expression in the differential diagnosis of hepatic actinomycosis: a case report

Guo

Gong

et al. 2013

J Med Case Reports

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IntroductionPrimary hepatic actinomycosis is a rare disease, but is important in the differential diagnosis of hepatoma in endemic areas. As high mobility group box chromosomal protein 1 plays an important role in the pathogenesis of both acute and chronic inflammatory conditions, we postulate that high mobility group box chromosomal protein 1 may have a possible pathogenic role in hepatic actinomycosis. To the best of our knowledge, our report is the first to detect an association between highly elevated high mobility group box chromosomal protein 1 expression and hepatic actinomycosis.Case presentationA 67-year-old Chinese man was admitted to our hospital with a three-month history of epigastric pain, anorexia, and subjective weight loss. Ultrasonography and computed tomography of the patient’s abdomen confirmed a hypodense mass measuring seven cm in diameter in the left lateral segment of his liver. A hepatic tumor was suspected and surgical resection was scheduled. Histopathologic examination revealed that the overall features of the hepatic tissues were consistent with hepatic actinomycosis. Whole blood and hepatic tissue samples of the patient, of patients who had hepatocellular carcinoma and of healthy donors were collected. Serum high mobility group box chromosomal protein 1 concentration in actinomycosis was 8.5ng/mL, which was higher than the hepatocellular carcinoma level of 5.2ng/mL and the normal level of

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Serum Levels of HMGB1 in Postmenopausal Patients with Rheumatoid Arthritis: Associations with Proinflammatory Cytokines, Acute-phase Reactants, and Clinical Disease Characteristics

Cited by 24 publications

References 10 publications

HMGB1 in health and disease

HMGB1 in health and disease

Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

The role of high mobility group box chromosomal protein 1 expression in the differential diagnosis of hepatic actinomycosis: a case report

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