The role of high mobility group protein B1 in rheumatic diseases

Abstract

High mobility group protein B1(HMGB1) is a non-histone nuclear protein. In addition to binding DNA and regulating the chromosomal architecture, it can also play a role as a damage associated molecular pattern that is involved in the pathological process in rheumatic diseases. Although it is mainly located in the nucleus, HMGB1 can be translocated into the cytoplasm and extracellular space during cell activation and cell death. With the redox state of the cysteine residues, HMGB1 activity is variable extracellularly, and Cys is required for TLR4 binding. Apart from directly stimulating cells, HMGB1 can form immune complexes with cytokines and other factors (endogenous and/or exogenous) to stimulate the receptors. In synovial fluid of rheumatoid arthritis patients and in animal models of the disease, the expression of HMGB1 is increased extranuclearly. Blockage of HMGB1 expression in animal models can alleviate the diseases. In systemic lupus erythematosus, HMGB1, which can interact with DNA, is an integral part of the immune complexes. All together, these findings suggest that HMGB1 can be an important mediator and biomarker in rheumatic diseases.It can also become a new valuable target for treating the diseases. Key words: High mobility group protein B1; Autoimmune disease; Rheumatic disease