Description
BoxA is one of the highly conserved DNA binding domains of HMGB1 protein (HMG boxes).
BoxA is an antagonist for HMGB1 binding to its receptor RAGE, and inhibits HMGB1 cytokine effects in vivo. The BoxA we provide has no difference from the sequence of the human or mouse HMGB1, and as a self-antigen elicits very low immunological responses. BoxA protects against sepsis in a mouse peritonitis model (Yang et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 2004, 101: 296-301), and from hepatitis in a mouse model of HBV infection (Sitia et al. Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice. J Leukoc Biol 2007, 81:100-7). Dendritic cells promote their own maturation and T cell proliferation, survival and Th1 differentiation by secreting HMGB1, and BoxA inhibits these activities (Dumitriu et al. Release of HMGB1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products (RAGE). J Immunol 2005, 174:7506-15). BoxA also inhibits the chemotactic activity of HMGB1 on endothelial cells and fibroblasts, and the mitogenic activity of HMGB1 for stem cells (ME Bianchi, unpublished).