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Horm Metab Res 2013; 45(04): 326-328
DOI: 10.1055/s-0032-1327643
Short Communication
© Georg Thieme Verlag KG Stuttgart · New York

Small Interfering-RNA to Protein Kinase C-Delta Reduces the Proinflammatory Effects of Human C-Reactive Protein in Biobreeding Diabetic Rats

I. Jialal
1   Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA, USA
2   Veterans Affairs Medical Center, Mather, CA, USA
,
A. Machha
1   Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA, USA
,
S. Devaraj
3   Texas Children’s Hospital and Baylor College of Medicine, Houston, TX, USA
› Author Affiliations
Further Information

Publication History

received 22 August 2012

accepted 20 September 2012

Publication Date:
26 October 2012 (online)

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Abstract

Type 1 diabetes (T1DM) is a proinflammatory state characterized by increased C-reactive protein (CRP) levels. Previously we reported that human CRP accentuated macrophage activity in spontaneously diabetic biobreeding (BB) rats and also increased protein kinase C (PKC) delta. Hence we tested the effect of molecular inhibition of PKC delta on plasma and macrophage proinflammatory biomarkers using small interfering (si)RNA to PKC delta. Prior to administration of human CRP, daily for 3 days to diabetic rats, scrambled siRNA or siRNA to PKC delta was also delivered for the 3 days, and the animals were sacrificed on day 4. Peritoneal macrophages and plasma were obtained. Compared to scrambled siRNA, siRNA to PKC delta resulted in a significant decrease in biomediators of inflammation in plasma and from macrophages (IL-1, TNF-alpha, IL-6, MCP-1, KC/IL-8, and PAI -1). However, siRNA to PKC delta has no effect on superoxide release from macrophages. In conclusion, our novel data suggests that siRNA to PKC delta attenuates the proinflammatory effect of human CRP in spontaneously diabetic BB rats and could have implications with regard to attenuating inflammation and vascular complications in T1DM.

 

  • References

  • 1 Schalkwijk CG, Poland DC, van Dijk W, Kok A, Emeis JJ, Drager AM, Doni A, van Hinsbergh VW, Stehouwer CD. Diabetologia 1999; 42: 351-357
    CrossrefPubMed
  • 2 Devaraj S, Glaser N, Griffen S, Wang-Polagruto J, Miguelino E, Jialal I. Diabetes 2006; 55: 774-779
    CrossrefPubMed
  • 3 Jialal I, Devaraj S. Cytokine 2012; 60: 318-320
    CrossrefPubMed
  • 4 Gibney J, Weis U, Turner B, Meeking DR, Cansfield J, Watts GF, Shaw KM, Cummungs MH. Diabetes Care 2002; 25: 802-803
    CrossrefPubMed
  • 5 Hansen TK, Forsblom C, Saraheimo M, Thorn L, Waden J, Hoyem P, Ostergaard J, Flyvbjerg A, Groop PH. FinnDiane Study Group . Diabetologia 2010; 53: 1517-1524
    CrossrefPubMed
  • 6 Jialal I, Kaur H, Devaraj S. J Diabetes Complications 2012; April 18 (Epub ahead of print) (PMID: 22520400)
    PubMed
  • 7 Jialal I, Devaraj S. Diab Vasc Dis Res 2012; 9: 315-319
    CrossrefPubMed
  • 8 Du Clos TW, Zlock LT, Marnell L. J Biol Chem 1991; 266: 2167-2171
    PubMed
  • 9 Devaraj S, Singh U, Jialal I. Clin Chem 2009; 55: 229-238
    PubMed
  • 10 Geraldes P, King GL. Circ Res 2010; 106: 1319-1331
    CrossrefPubMed