Ischemia-reperfusion injury has been associated with the incidence of both acute and chronic rejection. Together with the alloimmunone responses it is one of the most important causes of graft loss. Here, we test whether an anti-CD40 siRNA reduces kidney inflammation in a model of rat warm renal ischemia.
In the present study male Wistar rats were divided in 5 groups. SCR, group treated with scrambled siRNA(n=11); CD40-15, group treated with 15ug of siRNA(n=6); CD40-50, group treated with 50ug of siRNA(n=8); CD40-150, group treated with 150ug of siRNA(n=7) and CD40-500 group treated with 500ug of siRNA(n=6). The siRNA anti CD40 was administered 1hour before the ischemia. Ischemia was induced by clamping both renal pedicles for 40minutes, followed by reperfusion. Animals were followed up during 48hours.
Compared to scrambled controls, serum urea and creatinine levels were lower in treated groups. The histopathological analysis illustrates a renoprotective effect in those groups treated with higher doses of siRNA. Note that the highest dose of siRNA was the most effective reducing kidney interstitial infiltrate and tubular lesions. Analysis of kidney gene expression showed that there was no activation of innate immunity (TLR3) due to the siRNA molecule itself, and that the siRNA reduced CD40 and, also, proinflammatory cytokines such as IL4, IL2 and NFkB in treatment groups. Interstitial monocyte infiltrate (CD68+) showed a reduction in those kidneys with higher doses of siRNA treatment.
An additional study with ICR mice using only the 50ug dose showed similar functional and structural protection.
Systemic administration of a siRNA anti CD40 in models of ischemia-reperfusion injury was highly effective diminishing the molecular and cellular inflammatory response, improving serum urea and creatinine levels, and reducing tubular and interstitial lesions. Thus, the blockade of costimulatory signal CD40 becomes a potential therapeutic tool to modulate ischemia-reperfusion injury.
To cite this abstract in AMA style:Ramon Lde, Ripoll E, Luzardo L, Merino A, Lloberas N, Cruzado J, Grinyó J, Torras J. CD40 Gene Silencing Prevents Warm Renal Ischemia-Reperfusion Injury through Anti-Inflammatory Effects [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/cd40-gene-silencing-prevents-warm-renal-ischemia-reperfusion-injury-through-anti-inflammatory-effects/. Accessed May 28, 2020.
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