Ishwarlal Jialal1, Sridevi Devaraj. 1. Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, CA 95817, USA. ishwarlal.jialal@ucdmc.ucdavis.edu
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.
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 humanC-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 humanCRP on MOs in diabeticrats.
Authors: C G Schalkwijk; D C Poland; W van Dijk; A Kok; J J Emeis; A M Dräger; A Doni; V W van Hinsbergh; C D Stehouwer Journal: Diabetologia Date: 1999-03 Impact factor: 10.122
Authors: Sridevi Devaraj; Anthony T Cheung; Ishwarlal Jialal; Steven C Griffen; Danh Nguyen; Nicole Glaser; Thomas Aoki Journal: Diabetes Date: 2007-08-08 Impact factor: 9.461