High Mobility Group Box 1: a potential therapeutic target for systemic lupus erythematosus

  title={High Mobility Group Box 1: a potential therapeutic target for systemic lupus erythematosus},
  author={Hai-Feng Pan and Guo-Cui Wu and Weiping Li and Xiang-Pei Li and Dongqing Ye},
  journal={Molecular Biology Reports},
High Mobility Group Box 1 (HMGB1) is a nuclear protein participating in chromatin architecture and transcriptional regulation. Recently, there is increasing evidence that HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases due to its pro-inflammatory and immunostimulatory properties. Elevated expression of HMGB1 was found in the sera of patients and mice with systemic lupus erythematosus (SLE). In addition, it has been shown that HMGB1 may act as a… 

HMGB1 in health and disease.

Neutrophil extracellular traps are a source of extracellular HMGB1 in lupus nephritis: associations with clinical and histopathological features

The expression of HMGB1 in NETs is higher among patients with LN, which correlates with clinical and histopathological features of active nephritis and suggest a possible role of this alarmin in the pathophysiology of kidney damage in SLE.

Immune complexes activate human endothelium involving the cell-signaling HMGB1-RAGE axis in the pathogenesis of lupus vasculitis

It is demonstrated for the first time that ICs elicit proinflammatory responses in human endothelial cells and alter their function involving cellular signaling via the HMGB1-RAGE axis in the pathogenesis of SLE vasculitis.

TWEAK as a target for therapy in systemic lupus erythematosus

The TWEAK-Fn14 pathway and the therapeutic potential of modulating this pathway in SLE are discussed.

Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis

TAT-CLs-DHA/siRNA may have the potential for treatment of inflammatory diseases such as LN mediated by the TLR4 signaling pathway.

Level of secreted HMGB1 correlates with severity of inflammation in chronic rhinosinusitis

The purpose of this study was to determine the relationship between the HMGB1 level in nasal secretions and the severity of inflammation in chronic rhinosinusitis.

HMGB1 Localization during Experimental Periodontitis

It is demonstrated that HMGB1 may be associated with the onset and progression of periodontitis, suggesting that further studies should investigate the potential role ofHMGB1 on periodontal tissue destruction.

Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases

The autoimmune diseases linked to NETosis are reviewed, with a focus on how modified proteins externalized on NETs may trigger loss of immune tolerance and promote organ damage.



High mobility group box 1 in the pathogenesis of inflammatory and autoimmune diseases.

High mobility group box 1 appears to be crucially involved in the pathogenesis of arthritis since neutralization of HMGB1 significantly ameliorates the disease and in the serum and plasma of patients with systemic lupus erythematosus, it is detected substantial amounts ofHMGB1, which may contribute to the disease process.

Expression of high mobility group protein 1 in the sera of patients and mice with systemic lupus erythematosus

High mobility group protein 1 (HMGB1) is a non-histone nuclear protein with a dual function that is present in tissue in conditions, such as rheumatoid arthritis and cutaneous lupus and in animal models of sepsis and arthritis.

High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal

These features of HMGB1 are discussed and recent advances that have led to the preclinical development of therapeutics that modulateHMGB1 release and activity are summarized.

High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease

High-mobility group box protein 1 can play an important role in the pathogenesis of rheumatic disease, including rheumatoid arthritis, systemic lupus erythematosus, and polymyositis among others and new approaches to therapy for these diseases may involve strategies to inhibit HMGB1 release from cells, its interaction with receptors, and downstream signaling.

The cytokine activity of HMGB1

An abridged review of the cytokine activity of HMGB1, its secretion and release into the extracellular milieu, the putative signal transduction pathways, including interaction with cell‐surface receptors and intracellular signaling, and its role in several inflammatory diseases is given.

High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine.

HMGB-1 was more strongly expressed in SF of RA patients than in that of OA patients, inducing the release of proinflammatory cytokines from SFMs.

Factors masking HMGB1 in human serum and plasma

Sensitive ELISAs for the detection of high mobility group box 1 protein in cell culture medium and cell lysates are described, but these assays failed to reliably quantitate HMGB1 in serum and plasma when compared with immunoblot analysis.

HMGB1 as a cytokine and therapeutic target

Truncation of HMGB1 into individual structural domains revealed that the HM GB1 A box, a DNA-binding motif, specifically antagonizes the activity ofHMGB1 and rescues mice from lethal sepsis caused by cecal perforation.

Induction of inflammatory and immune responses by HMGB1–nucleosome complexes: implications for the pathogenesis of SLE

HMGB1–nucleosome complexes activate antigen presenting cells and, thereby, may crucially contribute to the pathogenesis of SLE via breaking the immunological tolerance against nucleosomes/dsDNA.

Reversing established sepsis with antagonists of endogenous high-mobility group box 1

  • Huan YangM. Ochani K. Tracey
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
Observations demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses lethality of established sepsis indicating thatHMGB1 inhibitors can be administered in a clinically relevant time frame.