Innate Immune Reactions Against RNA Viruses in Renal Mesangial Cells

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Viral infection is important in renal pathology both as a trigger of chronic inflammatory diseases and as a complication associated with organ transplantation. Glomerular mesangial cells produce a variety of functional molecules potentially involved in immune reactions, and we investigated anti-viral responses in normal human mesangial cells. Human mesangial cells were treated with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA that mimics viral RNA. Treatment of cells with poly IC induced interferon-β (IFN-β), retinoic acid-inducible gene-I( RIG-I), CC chemokine ligand 5( CCL5), differentiated embryo-chondrocyte 2( DEC2) and IFN-stimulated gene 20 (ISG20). Knockdown of toll-like receptor 3 (TLR3), by RNA interference (RNAi), abolished the poly IC-induced expression of these molecules. RNAi against IFN-β inhibited the induction of RIG-I, CCL5 and ISG20, but not of DEC2. Knockdown of RIG-I resulted in the reduced expression of CCL5. RNAi against DEC2 enhanced the poly IC-induced expression of IFN-β, RIG-I and CCL5. Transfection of cells with a poly IC/cationic lipid complex induced IFN-β, RIG-I and ISG20. Knockdown of RIG-I decreased the expression of IFN-β and ISG20 induced by transfection with poly IC/cationic lipid. TLR3 and RIG-I may function as recognition receptors against double-stranded RNA, which induce IFN-β and its downstream IFN-inducible genes. In the signaling elicited by poly IC, the IFN-inducible genes include RIG-I and effector molecules as CCL5 with leukocyte chemotactic activity and ISG20 with exonuclease activity on single-stranded RNA. The poly IC-induced expression of DEC2 is independent on IFN-β and it may control the signaling elicited by double-stranded RNA. The poly IC-inducible molecules may mediate anti-viral innate responses in renal mesangial cells.

弘前医学. 64(Suppl.), 2013, p.S70-73

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  • 弘前医学

    弘前医学 64 (Supplement), S70-S73, 2013-04-02

    弘前大学大学院医学研究科・弘前医学会

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