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

J Diabetes Complications. 2013 Jan-Feb;27(1):23-8. doi: 10.1016/j.jdiacomp.2012.03.020. Epub 2012 Apr 18.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • C-Reactive Protein / administration & dosage
  • C-Reactive Protein / pharmacology*
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / immunology*
  • Diabetes Mellitus, Experimental / metabolism
  • Humans
  • Inflammation / complications
  • Inflammation / immunology
  • Inflammation / metabolism
  • Macrophage Activation / drug effects*
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / physiology
  • Male
  • Rats
  • Rats, Inbred BB

Substances

  • Chemokines
  • Cytokines
  • C-Reactive Protein