The role of high mobility group box chromosomal protein 1 in rheumatoid arthritis

Abstract

High mobility group box chromosomal protein 1 (HMGB1) is a ubiquitous highly conserved single polypeptide in all mammal eukaryotic cells. HMGB1 exists mainly within the nucleus and acts as a DNA chaperone. When passively released from necrotic cells or actively secreted into the extracellular milieu in response to appropriate signal stimulation, HMGB1 binds to related cell signal transduction receptors, such as RAGE, TLR2, TLR4 and TLR9, and becomes a proinflammatory cytokine that participates in the development and progression of many diseases, such as arthritis, acute lung injury, graft rejection immune response, ischaemia reperfusion injury and autoimmune liver damage. Only a small amount of HMGB1 release occurs during apoptosis, which undergoes oxidative modification on Cys106 and delivers tolerogenic signals to suppress immune activity. This review focuses on the important role of HMGB1 in the pathogenesis of RA, mainly manifested as the aberrant expression of HMGB1 in the serum, SF and synovial tissues; overexpression of signal transduction receptors; abnormal regulation of osteoclastogenesis and bone remodelling leading to the destruction of cartilage and bones. Intervention with HMGB1 may ameliorate the pathogenic conditions and attenuate disease progression of RA. Therefore administration of an HMGB1 inhibitor may represent a promising clinical approach for the treatment of RA.

Overexpression of Receptor for Advanced Glycation End Products and High-Mobility Group Box 1 in Human Dental Pulp Inflammation

“…Concentrations of LPS used for HMGB1 stimulation in this study were not cytotoxic to OLC-1 cells (data not shown). Our results on changes in HMGB1 in OLC-1 cells are consistent with those of previous studies in which HMGB1 is actively secreted from LPS-activated immune and nonimmune cells involved in chronic inflammatory diseases [50–52]. Furthermore, HMGB1 was solely localized in the nucleus of odontoblasts in healthy tissues, while a significant proportion of HMGB1 translocated to the cytoplasm in pulpitis tissue, which correlates with an increase in extracellular HMGB1 in LPS stimulated OLC-1 cells.…”

Anti‐Toll‐like receptor 2 and 4 antibodies suppress inflammatory response in mice

“…Furthermore, the antibody treatments reduced the production of key pro‐inflammatory cytokines, IL‐12 and TNF‐ α , which play a pathogenic role in many pro‐inflammatory and autoimmune diseases . This is consistent with previous reports that TLR2 and TLR4 signals are generally pro‐inflammatory in other inflammatory arthritis models and suggests that the anti‐inflammatory effect observed here may extend beyond CIA to other inflammatory disorders . While the detailed mechanisms are still unknown, the neutralizing antibodies could block the TLRs‐mediated effects by directly antagonizing the ligand/TLRs interaction in the arthritic context.…”

“…While the detailed mechanisms are still unknown, the neutralizing antibodies could block the TLRs‐mediated effects by directly antagonizing the ligand/TLRs interaction in the arthritic context. The possible TLR2 ligands may include the endogenous gp96 and serum amyloid A and extraneous mycobacteria components present in the complete adjuvant . Possible TLR4 ligands may be the endogenous fibrinogen, hyaluronic acid and HMGB‐1 and exogenous LPS, which are present in vivo and proven important for the induction of CIA …”

IL‐1β mediating high mobility group box protein‐1 expression in condylar chondrocyte during temporomandibular joint inflammation

“…Previous studies had demonstrated that acetylation and phosphorylation of HMGB‐1 regulated HMGB‐1 transporting to the cytoplasm . In monocytes, a non‐classical vesicle compartment‐mediated pathway and exocytosis of secretory lysosomes had regulated the HMGB‐1 transporting to extracellular matrix .…”