Article

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; VA Medical Center, Mather, CA, USA.
Journal of diabetes and its complications (Impact Factor: 2.11). 04/2012; 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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