Inflammation Promoting Activity Of HMGB-1 In Type-II Diabetes And As a Marker Of Tissue Injury . (54.3)

Abstract HMGB-1 is a well characterized DNA-binding protein and a potent proinflammatory molecule when released extracellularly during tissue injury. Accelerated atherosclerosis is a major cause of morbidity in diabetes and a causative factor of coronary artery disease, stroke and vascular disease. HMGB-1 is elevated in ischemia-reperfusion injury of the heart and also highly expressed in endothelial cells, vascular smooth muscles, and macrophages present in atherosclerotic lesions. Since HMGB1 is a ligand for advanced glycation end products (RAGE) and is capable of interacting with toll-like receptors, it is likely that a vicious cycle of pro-inflammatory activity occur in patients with diabetes. In this study, the role of HMGB-1 in type II patients (T2D) was examined to better understand its role in chronic inflammation. Plasma samples from T2D patients (n=13) and age matched healthy normal controls (n=20) were analyzed for HMGB-1 and proinflammatory cytokines IL-6 and TNF-α. Our results showed that patients with T2D had significantly elevated levels of TNF-α and IL-6 as compared to healthy controls. Elevated levels of pro-inflammatory cytokines also correlate well with HMGB-1 levels found in patient sera. Collectively, our data suggests a pro-inflammatory activity in patients with T2D. Endogenous danger signals such as HMGB-1 may promote autocrine loop of inflammation and contribute to the persistence of inflammation in type II diabetes and autoimmune diseases.