Roma Pahwa1, Ishwarlal Jialal2. 1. Laboratory of Atherosclerosis and Metabolic Research, Department of Pathology and InternalMedicine, University of California Davis Medical Center, Sacramento, CA. 2. Laboratory of Atherosclerosis and Metabolic Research, Department of Pathology and InternalMedicine, University of California Davis Medical Center, Sacramento, CA; Medical Services (Endocrinology and Metabolism), VA Medical Center, Mather, CA. Electronic address: ijialal@ucdavis.edu.
Abstract
OBJECTIVES: Increased Toll like receptors (TLRs) especially 2 and 4 have been demonstrated in obesity, metabolic syndrome (MetS) and diabetes resulting in increased cellular inflammation. Since we have shown increased TLR2 and 4 activities in both T1DM and T2DM and MetS, we wanted to elucidate the mechanisms of this sterile inflammation. In T1DM, T2DM and MetS we have shown that high mobility group box 1 protein (HMGB-1), a non-histone DNA binding protein is increased and could be a potential activator of TLRs since it has previously shown to activate TLR2, 4 and 9. We examined the role of HMGB-1 in patients and animal models of diabetes and MetS to determine how important it is as an activator of TLR mediated inflammation and its role in diabetic vascular complications. METHODS: A Medline search was conducted using the terms HMGB-1, TLRs and diabetes. RESULTS: HMGB-1 levels are increased in patients with diabetes and MetS, and associated with increased biomediators of inflammation. Furthermore data supported a role of HMGB-1 in both diabetic microvascular and macrovascular complications. CONCLUSIONS: HMGB-1 interaction with TLRs is implicated in diabetic complications and could be important therapeutic target. Published by Elsevier Inc.
OBJECTIVES: Increased Toll like receptors (TLRs) especially 2 and 4 have been demonstrated in obesity, metabolic syndrome (MetS) and diabetes resulting in increased cellular inflammation. Since we have shown increased TLR2 and 4 activities in both T1DM and T2DM and MetS, we wanted to elucidate the mechanisms of this sterile inflammation. In T1DM, T2DM and MetS we have shown that high mobility group box 1 protein (HMGB-1), a non-histone DNA binding protein is increased and could be a potential activator of TLRs since it has previously shown to activate TLR2, 4 and 9. We examined the role of HMGB-1 in patients and animal models of diabetes and MetS to determine how important it is as an activator of TLR mediated inflammation and its role in diabetic vascular complications. METHODS: A Medline search was conducted using the terms HMGB-1, TLRs and diabetes. RESULTS:HMGB-1 levels are increased in patients with diabetes and MetS, and associated with increased biomediators of inflammation. Furthermore data supported a role of HMGB-1 in both diabetic microvascular and macrovascular complications. CONCLUSIONS:HMGB-1 interaction with TLRs is implicated in diabetic complications and could be important therapeutic target. Published by Elsevier Inc.