Polyinosinic-polycytidylic acid induces the expression of interferon-stimulated gene 20 in mesangial cells.

BACKGROUND/AIMS: Interferon (IFN)-stimulated gene 20 (ISG20) is a 3'-to-5' exonuclease specific for single-stranded RNA and involved in host defense reactions against RNA viruses. The expression and the role of ISG20 in mesangial cells have not been reported.

METHODS

Normal human mesangial cells were cultured and treated with polyinosinic-polycytidylic acid (poly (I:C)), an authentic double-stranded RNA which mimics viral infection to cells. The effect of RNA interference of Toll-like receptor 3 (TLR3) or IFN-β on the ISG20 expression was examined. The effect of a blocking antibody against the receptor for IFN-β or anti-inflammatory steroid dexamethasone was also examined.

RESULTS

Treatment of cells with poly (I:C) induced the expression of ISG20. The poly (I:C)-induced expression of ISG20 was inhibited by knockdown of TLR3, IFN regulatery factor 3 (IRF3) or IFN-β. Blocking of the receptor for IFN-β suppressed and overexpression of IFN-β enhanced ISG20 expression. The poly (I:C)-induced expressions of IFN-β and ISG20 were inhibited by dexamethasone. Transfection of mesangial cells with poly (I:C) or 5'-triphosphate single-stranded RNA as a complex with cationic lipid also induced the expression of ISG20, and this was inhibited by knockdown of retinoic acid-inducible gene-I (RIG-I).

CONCLUSION

Poly (I:C) induces the expression of ISG20 in mesangial cells. ISG20 may be involved in anti-viral reactions in renal mesangial cells. TLR3, IRF3 and de novo synthesized IFN-β may mediate the poly (I:C)-induced expression of ISG20, and RIG-I may mediate ISG20 expression induced by poly (I:C)/cationic lipid complex.