[Role of HMGB1 in rheumatic diseases]

Abstract

High mobility group box chromosomal protein 1 (HMGB1) is originally identified as a DNA-binding protein that functions as a structural co-factor. HMGB1 is actively secreted by macrophage/monocytes via inflammatory stimuli. The extracellular HMGB-1 acts as a mediator of acute and chronic systematic inflammation. In this article we briefly review its role in rheumatic diseases: arthritis, polymyositis and dermatomyositis, lupus erythematosus and Sjogren's syndrome. Increased cytoplasmic expression and extracellular deposition of HMGB1 are found in the affected tissues of those diseases, especially stronger in/around focal infiltrates of mononuclear cells. TNFalpha and IL-1beta are co-expressed in areas of extracellular HMGB1. HMGB1 together with TNF alpha and IL-1beta may form a proinflammatory loop promoting the chronic inflammations. The new findings of HMGB1 as a cytokine provide a better understanding of rheumatiod diseases, and could become a clinically relevant therapeutic target that might be more efficient than other known cytokines.