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

Ishwarlal Jialal, Harmeet Kaur, Sridevi Devaraj

Research output: Contribution to journalArticle

7 Scopus citations

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 (M∅) 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 M∅ 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.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalJournal of Diabetes and its Complications
Volume27
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • C-reactive protein
  • Macrophages
  • NF-κB
  • p47Phox
  • PAI-1
  • PKC
  • Tissue factor

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

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