Ishwarlal Jialal1, Harmeet Kaur, Sridevi Devaraj. 1. Laboratory of Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, CA, USA. ishwarlal.jialal@ucdmc.ucdavis.edu
Abstract
OBJECTIVE: Type 1 diabetes (T1DM) is a pro-inflammatory state characterized by high C-reactive protein (CRP) levels. However, there is a paucity of data examining the role of CRP in promoting the pro-inflammatory state of diabetes. Thus, we examined the pro-inflammatory effects of human CRP using spontaneously diabetic bio-breeding (BB) rats. METHODS: Diabetic rats (n=9/group) were injected with Human serum albumin (huSA) or Human CRP (hCRP, 20 mg/kg body weight; i.p.) for 3 consecutive days. Blood and peritoneal macrophages (MØ) were obtained following euthanasia. Peritoneal macrophages were used for measuring superoxide anion release, NF-κB DNA binding activity, proinflammatory mediator secretion. RESULTS: hCRP administration resulted in significantly increased superoxide anion production, along with increased release of cytokines/chemokines, and plasminogen activator inhibitor (PAI-1) and Tissue Factor (TF) activity in diabetic rats compared to huSA. hCRP-treated BB rat MØ showed significant induction of protein kinase C (PKC)-alpha, PKC-delta and p47 phox expression and NF-κB compared to huSA. CONCLUSIONS: Thus, our data suggest that human CRP exacerbates in-vivo the pro-inflammatory, pro-oxidant and procoagulant states of diabetes predominantly via increased macrophage activity and this could have implications with respect to vascular complications and anti-inflammatory therapies. Published by Elsevier Inc.
OBJECTIVE:Type 1 diabetes (T1DM) is a pro-inflammatory state characterized by high C-reactive protein (CRP) levels. However, there is a paucity of data examining the role of CRP in promoting the pro-inflammatory state of diabetes. Thus, we examined the pro-inflammatory effects of humanCRP using spontaneously diabetic bio-breeding (BB) rats. METHODS:Diabeticrats (n=9/group) were injected with Humanserum albumin (huSA) or HumanCRP (hCRP, 20 mg/kg body weight; i.p.) for 3 consecutive days. Blood and peritoneal macrophages (MØ) were obtained following euthanasia. Peritoneal macrophages were used for measuring superoxide anion release, NF-κB DNA binding activity, proinflammatory mediator secretion. RESULTS:hCRP administration resulted in significantly increased superoxide anion production, along with increased release of cytokines/chemokines, and plasminogen activator inhibitor (PAI-1) and Tissue Factor (TF) activity in diabeticrats compared to huSA. hCRP-treated BBrat MØ showed significant induction of protein kinase C (PKC)-alpha, PKC-delta and p47 phox expression and NF-κB compared to huSA. CONCLUSIONS: Thus, our data suggest that humanCRP exacerbates in-vivo the pro-inflammatory, pro-oxidant and procoagulant states of diabetes predominantly via increased macrophage activity and this could have implications with respect to vascular complications and anti-inflammatory therapies. Published by Elsevier Inc.
Authors: K M Venkat Narayan; James P Boyle; Theodore J Thompson; Stephen W Sorensen; David F Williamson Journal: JAMA Date: 2003-10-08 Impact factor: 56.272
Authors: Matthias B Schulze; Eric B Rimm; Tricia Li; Nader Rifai; Meir J Stampfer; Frank B Hu Journal: Diabetes Care Date: 2004-04 Impact factor: 19.112