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

Author:

Jialal Ishwarlal12,Devaraj Sridevi3

Affiliation:

1. Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, CA, USA

2. Department of Medicine, VA Medical Center, Mather, CA, USA

3. Department of Pathology and Immunology, Baylor College of Medicine, and Texas Children’s Hospital, Houston, TX, USA

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.

Publisher

SAGE Publications

Subject

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

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