Successful treatment of collagen-induced arthritis in mice and rats by targeting extracellular high mobility group box chromosomal protein 1 activity

2003 ◽  
Vol 48 (7) ◽  
pp. 2052-2058 ◽  
Author(s):  
R. Kokkola ◽  
J. Li ◽  
E. Sundberg ◽  
A.-C. Aveberger ◽  
K. Palmblad ◽  
...  
Keyword(s):  
Successful Treatment ◽  
High Mobility ◽  
High Mobility Group ◽  
Chromosomal Protein ◽  
Collagen Induced Arthritis

High Mobility Group Box Chromosomal Protein-1 Induces Myofibroblast Differentiation and Extracellular Matrix Production via RAGE, p38, JNK and AP-1 Signaling Pathways in Nasal Fibroblasts

2021 ◽  
pp. 194589242199814
Author(s):  
Soo-Hyung Lee ◽  
Jae Hoon Cho ◽  
Joo-Hoo Park ◽  
Jung-Sun Cho ◽  
Heung-Man Lee
Keyword(s):  
Extracellular Matrix ◽  
Chronic Rhinosinusitis ◽  
Smooth Muscle Actin ◽  
High Mobility ◽  
Signal Pathway ◽  
High Mobility Group ◽  
Myofibroblast Differentiation ◽  
Chromosomal Protein ◽  
Protein Levels ◽  
Matrix Production

Background Chronic rhinosinusitis is involved in myofibroblast differentiation and extracellular matrix (ECM) accumulation. High mobility group box chromosomal protein 1 (HMGB-1) is known to stimulate lung fibroblast to produce ECM in lung fibrosis. The aim of this study was to investigate whether HMGB-1 induces myofibroblast differentiation and ECM production in nasal fibroblasts and to identify the signal pathway. Methods Human nasal fibroblasts were cultured. After stimulation with HMGB-1, expressions of α-smooth muscle actin (α-SMA) and fibronectin were determined by real-time PCR and western blot. Total collagen was measured by Sircol assay. To investigate signal pathway, various signal inhibitors and RAGE siRNA were used. Results HMGB-1 increased α-SMA and fibronectin in mRNA and protein levels. It also increased collagen production. RAGE siRNA inhibited HMGB-1-induced α-SMA and fibronectin, and production of collagen. Furthermore, the inhibitors of RAGE downstream molecules such as p38, JNK and AP-1 also blocked the HMGB-1-induced effects. Conclusions HMGB-1 induces myofibroblast differentiation and ECM production in nasal fibroblast, which is mediated by RAGE, p38, JNK and AP-1 signal pathway. These results suggest that HMGB-1 may play an important role in tissue remodeling during chronic rhinosinusitis progression.

scholarly journals Does high-mobility-group non-histone protein HMG 1 interact specifically with histone H1 subfractions?

1979 ◽  
Vol 183 (3) ◽  
pp. 657-662 ◽  
Author(s):  
P D Cary ◽  
K V Shooter ◽  
G H Goodwin ◽  
E W Johns ◽  
J Y Olayemi ◽  
...  
Keyword(s):  
Specific Interaction ◽  
High Mobility ◽  
Histone H1 ◽  
High Mobility Group ◽  
Chromosomal Protein ◽  
Histone Protein ◽  
Total Histone ◽  
Equilibrium Sedimentation ◽  
Histone H5

The interaction of the non-histone chromosomal protein HMG (high-mobility group) 1 with histone H1 subfractions was investigated by equilibrium sedimentation and n.m.r. sectroscopy. In contrast with a previous report [Smerdon & Isenberg (1976) Biochemistry 15, 4242–4247], it was found, by using equilibrium-sedimentation analysis, that protein HMG 1 binds to all three histone H1 subfractions CTL1, CTL2, and CTL3, arguing against there being a specific interaction between protein HMG 1 and only two of the subfractions, CTL1 and CTL2. Raising the ionic strength of the solutions prevents binding of protein HMG 1 to total histone H1 and the three subfractions, suggesting that the binding in vitro is simply a non-specific ionic interaction between acidic regions of the non-histone protein and the basic regions of the histone. Protein HMG 1 binds to histone H5 also, supporting this view. The above conclusions are supported by n.m.r. studies of protein HMG 1/histone H1 subfraction mixtures. When the two proteins were mixed, there was little perturbation of the n.m.r. spectra and there was no evidence for specific interaction of protein HMG 1 with any of the subfractions. It therefore remains an open question as to whether protein HMG 1 and histone H1 are complexed together in chromatin.

Expression of High Mobility Group Box Chromosomal Protein 1 and Its Modulating Effects on Downstream Cytokines in Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (4) ◽  
pp. 766-775 ◽  
Author(s):  
JIE LI ◽  
HONGFU XIE ◽  
TING WEN ◽  
HONGBO LIU ◽  
WU ZHU ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Messenger Rna ◽  
Activity Index ◽  
High Mobility ◽  
High Mobility Group ◽  
Chromosomal Protein ◽  
Systemic Lupus ◽  
Tnf Α

Objective.To compare the expression of high mobility group box chromosomal protein 1 (HMGB1) and the modulating effects on its downstream cytokines in patients with systemic lupus erythematosus (SLE) and healthy controls.Methods.HMGB1 concentrations in serum from SLE patients and controls were measured by immunoblot analysis. HMGB1 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) was detected by real-time reverse transcription–polymerase chain reaction. Immunofluorescence assay was employed to examine the translocation of HMGB1 in monocytes after endotoxin stimulation. Release of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) by PBMC after rHMGB1 stimulation was also measured.Results.Serum HMGB1 levels and HMGB1 mRNA expressions in PBMC were elevated in SLE patients compared with controls. A positive correlation was demonstrated between HMGB1 concentrations and SLE Disease Activity Index. There was an inverse correlation between HMGB1 levels and C4 and C3 concentrations in SLE patients. HMGB1 concentrations were higher in patients with vasculitis and myositis. Lipopolysaccharide stimulated a temporarily elevated release of HMGB1 in SLE patients compared with controls. The pattern and localization of HMGB1 staining in monocytes were similar in both groups. After stimulation with rHMGB1, TNF-α level decreased but IL-6 level increased in SLE patients compared with controls.Conclusion.Our findings suggest that increased serum levels of HMGB1 in SLE may be associated with lupus disease activity. The altered production of TNF-α and IL-6 in response to rHMGB1 stimulation may participate in the disruption of cytokine homeostasis in SLE.

High Mobility Group Box Chromosomal Protein 1 in Patients with Renal Diseases

2008 ◽  
Vol 108 (3) ◽  
pp. c194-c201 ◽  
Author(s):  
Fumihiko Sato ◽  
Shoichi Maruyama ◽  
Hiroki Hayashi ◽  
Izumi Sakamoto ◽  
Shingo Yamada ◽  
...  
Keyword(s):  
High Mobility ◽  
High Mobility Group ◽  
Renal Diseases ◽  
Chromosomal Protein

Anti-High-Mobility Group Box Chromosomal Protein 1 Antibodies Improve Survival of Rats with Sepsis

2006 ◽  
Vol 30 (9) ◽  
pp. 1755-1762 ◽  
Author(s):  
Koichi Suda ◽  
Yuko Kitagawa ◽  
Soji Ozawa ◽  
Yoshiro Saikawa ◽  
Masakazu Ueda ◽  
...  
Keyword(s):  
High Mobility ◽  
High Mobility Group ◽  
Chromosomal Protein

Increase of High-Mobility Group Box Chromosomal Protein 1 in Blood and Injured Organs in Experimental Severe Acute Pancreatitis

Pancreas ◽  
2007 ◽  
Vol 34 (4) ◽  
pp. 487-488 ◽  
Author(s):  
Takeo Yasuda ◽  
Takashi Ueda ◽  
Makoto Shinzeki ◽  
Hidehiro Sawa ◽  
Takahiro Nakajima ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
High Mobility ◽  
High Mobility Group ◽  
Chromosomal Protein

High-mobility group box-1 protein induce inflammatory response after pulmonary injury

2015 ◽  
Vol 3 (3) ◽  
pp. 195-214
Author(s):  
Jingxian H Golemis ◽  
Laurie J Rudensky
Keyword(s):  
Lung Injury ◽  
Inflammatory Response ◽  
Intratracheal Instillation ◽  
High Mobility ◽  
Lavage Fluid ◽  
High Mobility Group ◽  
Saline Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Chromosomal Protein

High-mobility group box 1 (HMGB1), a highly conserved non-histone chromosomal protein, was found to act as a potent proinflammatory cytokine and a mediator that participated in the development of systemic inflammatory response. Forty wild type C57BL/6 male (25-30gms) mice were randomly divided into three groups: saline control group; anti-HMGB1 antibody treated group and untreated group. Each group received intratracheal instillation twice per week for 4 consecutive months. 24 hours after the last exposure, anaesthetize the mice with chloral hydrate, bronchoalveolar lavage fluid was collected for cytokines analysis were measured by enzyme linked immunosorbent assay (ELISA). The level of the HMGB1 in lung tissue was determined by real-time PCR and western blot. Lung were fixed with 4% paraformaldehyde for histopathological detection. The serum level of HMGB1 increased after lung injury [peaked 2-5 hr] after lung injury, furthermore this upregulation in HMGB1 associated with increased proinflammatory cytokines [TNF-α, IL-6, IL-1β]. The injection of anti-HMGB1 antibody suppressed inflammatory reaction and improved the survival rate compared with control mice [71.3% vs. 29.4% P=0.031]

scholarly journals Monoclonal Anti-HMGB1 (High Mobility Group Box Chromosomal Protein 1) Antibody Protection in Two Experimental Arthritis Models

2011 ◽  
Vol 17 (9-10) ◽  
pp. 1039-1044 ◽  
Author(s):  
Hanna Schierbeck ◽  
Peter Lundbäck ◽  
Karin Palmblad ◽  
Lena Klevenvall ◽  
Helena Erlandsson-Harris ◽  
...  
Keyword(s):  
High Mobility ◽  
Experimental Arthritis ◽  
High Mobility Group ◽  
Chromosomal Protein ◽  
Arthritis Models
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