title: Small interfering-RNA to protein kinase C-delta reduces the proinflammatory effects of human C-reactive protein in biobreeding diabetic rats.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA, USA. Ishwarlal.jialal@ucdmc.ucdavis.edu
authors.forename: I
authors.initials: I
authors.lastname: Jialal
authors.forename: A
authors.initials: A
authors.lastname: Machha
authors.forename: S
authors.initials: S
authors.lastname: Devaraj
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001947:Breeding; D002097:C-Reactive Protein / Q000009:adverse effects / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced; D018836:Inflammation Mediators / Q000097:blood*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D017395:Plasminogen Activator Inhibitor 1; D034741:RNA, Small Interfering; D013481:Superoxides; D002097:C-Reactive Protein; C497260:Prkcd protein, rat; D051745:Protein Kinase C-delta