Antisense to protein kinase C-alpha and p47phox attenuates the pro-inflammatory effects of human C-reactive protein in macrophages of biobreeding diabetic rats

Ishwarlal Jialal, Sridevi Devaraj

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Objective: Type 1 diabetes mellitus (T1DM) is a pro-inflammatory state characterized by high C-reactive protein (CRP) levels. Previously, we showed that CRP accentuated a macrophage (MO) activity in spontaneously diabetic biobreeding (BB) rats and increased the MO activity of protein kinase C-alpha (PKC-α) and p47phox. In this report, we tested the effects of molecular inhibition of CRP effects on MO activity using antisense oligonucleotide (ASO) to both PKC-α and p47phox. Methods: Prior to administration of human C-reactive protein (hCRP) daily for 3 days, ASO or scrambled ASO to either PKC-α or p47phox was also delivered for 3 days and after killing on day 4, peritoneal MOs were isolated. Results: The increase in the levels of superoxide anion, interleukin (IL)-1, monocyte chemoattractant protein-1 (MCP-1), tumour necrosis factor-alpha (TNF-α) and IL-6 release in MOs with hCRP compared to human albumin was significantly attenuated by antisense to either PKC-α and p47phox (p < 0.01 vs. scrambled ASO; n = 5 per group). Conclusion: Our novel data suggest that antisense to either PKC-α or p47phox attenuates the pro-inflammatory effects of human CRP on MOs in diabetic rats.

Original languageEnglish (US)
Pages (from-to)315-319
Number of pages5
JournalDiabetes and Vascular Disease Research
Volume9
Issue number4
DOIs
StatePublished - Oct 2012

Keywords

  • C-reactive protein
  • cytokines
  • macrophages
  • p47phox
  • protein kinase C
  • superoxide

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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