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Journal 'Cytokines & inflammation', 2008, No. 1

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Original Articles

Number 1'2008

THE CHANGES IN REGULATORY FUNCTION OF DENDRITIC CELLS AFTER ADMINISTRATIONOF SHORT INTERFERENCE RNA FOR IL?12P35 GENE

T.E. Ichim, I.A. Popov, E.K. Oleinik

Dendritic cells (DC) play a key role in immune regulation since possesses the ability both to stimulate and inhibit various types of immune responses, depending on activation stimuli. We describe here the induction of RNA interference in bone marrow-derived DC by specific gene silencing with short strands of duplex RNA (small interfering RNA or siRNA) that target the cognate mRNA sequence for degradation. We demonstrate that transfection of DC with siRNA specific for the IL?12p35 gene resulted in suppression of gene expression and blockade of IL?12p70 production. Inhibition of IL?12 was associated with increased IL?10 production and with suppressed DC allostimulatory function. The Th2 polarization was observed when IL?12p35-treated DC were cultured with allogenic T cells since T cell expression of was reduced while IL?4 was increased. These data show that the switching immune response from Th1 to Th2 releases through an IL?10 dependent mechanism by administration of siRNA. The modulating of DC function possesses therapeutic potential and can be used effectively to treat a variety of immune diseases. (Cytokines and Inflammation. 2008. Vol. 7, No. 1. P. 29-34.)

Keywords: dendritic cells, gene silencing, RNA interference, siRNA, cytokines.

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