Retinoic acid-inducible gene-I is induced by double-stranded RNA and regulates the expression of CC chemokine ligand (CCL) 5 in human mesangial cells.

BACKGROUND: Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase involved in immune reactions against RNA viruses and various inflammatory and autoimmune diseases. The purpose of the present study was to investigate the role of RIG-I in glomerular diseases. METHODS: We treated human mesangial cells in culture with polyinosinic-polycytidylic acid (poly IC), which is an authentic double-stranded RNA, and analysed the expression of RIG-I, CC chemokine ligand 5 (CCL5) and interferon (IFN)-ß by western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) or enzyme-linked immunosorbent assay (ELISA). To elucidate the poly IC-signalling pathway, we subjected the cells to RNA interference (RNAi) against RIG-I, IFN-ß or Toll-like receptor (TLR) 3. Furthermore, we studied the effects of IFN-ß receptor blocking and IFN-ß overexpression. RESULTS: Poly IC induced the expression of RIG-I and CCL5 in human mesangial cells, and RNAi against RIG-I inhibited this poly IC-induced CCL5 expression. Poly IC-induced RIG-I expression was also inhibited by RNAi against IFN-ß and by an antibody against the IFN-ß receptor. IFN-ß overexpression induced the expression of both RIG-I and CCL5. The knockdown of TLR3 abolished poly IC-induced RIG-I expression. CONCLUSIONS: The TLR3/IFN-ß/RIG-I/CCL5 signalling pathway may mediate immune and inflammatory responses against viral infection in mesangial cells, suggesting the role of this pathway in the aggravation of glomerulonephritis due to viral infection.