title: Human C-reactive protein accentuates macrophage activity in biobreeding diabetic rats.
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.
authors.affiliation: 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
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
authors.forename: Harmeet
authors.initials: H
authors.lastname: Kaur
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000008:administration & dosage / Q000494:pharmacology*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB
chemical_list: D018925:Chemokines; D016207:Cytokines; D002097:C-Reactive Protein