Exploring the therapeutic promise of targeting HMGB1 in rheumatoid arthritis

International audienceHigh mobility group box-1 (HMGB1) protein is a diverse, single polypeptide moiety, present in mammalianeukaryotic cells. In response to stimuli, this nuclear protein is actively secreted in to the extracellular compartment or passively released by the necrotic cells, in order to mediate inflammatory responses, by formingcomplexes with IL-1α, IL-1β, LPS and other moieties, and binding to RAGE, TLR and other receptor ligands,initiating downstream, signaling processes. This molecule acts as a proinflammatory cytokine and contributes tothe progression of diseases like, acute lung injury, autoimmune liver damage, graft rejection immune responseand arthritis. Small concentrations of HMGB1 are released during apoptosis, which facilitates oxidative regulation on Cys106, and propagates immune inactivating tolerogenic signals in the body. The review portrays therole of HMGB1 in rheumatoid arthritis, evidently supported by pre-clinical and clinical investigations, demonstrating extensive HMGB1 expression in synovial tissue and fluid as well as serum, excessive expression oftransduction receptor signaling molecules, bone remodeling and uncontrolled expression of bone destroyingosteoclastogenesis, resulting in destruction of articular cartilage, bone deformation and synovial proliferation,alleviating the pathogenesis in RA disease. Moreover, the review highlights the therapeutic regime targetingHMGB1, facilitating inhibition of its actions and release into the extracellular compartment, to ameliorate thedestructive events that prevail in rheumatoid arthritis