Role of High-Mobility Group Box 1 (HMGB1) in Transplantation of Rat Pancreatic Islets.

Abstract

BACKGROUND The potential role of tissue damage factor high-mobility group box 1 (HMGB1) in islet cell transplantation is poorly understood. We investigated the role of HMGB1 in pancreatic islet cell isolation and culture in vitro and after pancreatic islet cell transplantation into diabetic nude mice in vivo. MATERIAL AND METHODS To generate damaged islets, isolated islets were treated with 1 mg/mL lipopolysaccharide (LPS). Some islets were pretreated with a neutralizing anti-HMGB1 antibody before LPS treatment to investigate the effect of HMGB1 on isolated islets damaged by LPS. Cell viability and insulin secretory function were analyzed 48 h after LPS and anti-HMGB1 antibody treatment. Streptozotocin-induced diabetes mice were injected with an anti-HMGB1 antibody 1 h prior to transplantation as a marginal islet mass. After transplantation, blood glucose levels were measured. RESULTS HMGB1 was more abundant in isolated islets than in other tissues, including pancreatic tissue. Anti-HMGB1 antibody pretreatment in LPS-treated islets improved cell viability and insulin secretory function and reduced the production of TNF-α and IL-1β. Streptozotocin-induced diabetic mice treated with an anti-HMGB1 antibody after marginal mass islet cell transplantation recovered to normal blood glucose levels more rapidly and maintained their euglycemic status compared to controls. CONCLUSIONS HMGB1 plays a significant role in early loss of transplanted islet cells. Based on these results, the development of new drugs that inhibit HMGB1 secretion could improve the efficacy and efficiency of clinical islet cell transplantation.