Human C-reactive protein accentuates macrophage activity in biobreeding diabetic rats

Laboratory of Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, CA, USA
Journal of diabetes and its complications (Impact Factor: 1.93). 04/2012; 27(1). DOI: 10.1016/j.jdiacomp.2012.03.020
Source: PubMed

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, 20mg/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.

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