The human bronchial epithelial cells are the primary sites of influenza virus
infection. In this study, the effect of
indirubin on the expression of the
chemokine regulated on activation, normal T cell expressed and secreted (
RANTES) by the influenza virus-infected H292 human epithelial cell line was examined. The expression of
RANTES mRNA was analyzed using reverse transcription polymerase chain reaction and the concentration of
RANTES production was determined by the
enzyme-linked
immunosorbent assay. At the non-cytotoxic concentrations,
indirubin was found to reduce both the expression and production of
RANTES in
influenza A/NWS/33-infected H292 cells. Inhibition was also observed in influenza virus B/Lee-infected cells. Significant reduction of the expression of
IL-8 was not observed after the
infection. Indirubin-3'-oxime, a recently developed derivative with
kinase inhibitory activity, also mediates a potent inhibitory effect on the expression of
RANTES. The influenza virus
infection-induced phosphorylation of the nuclear transcription
NF-kB regulatory molecule IkBalpha and the
p38 MAP kinase were also found to be inhibited by indirubin-3'-oxime. This finding suggests that
indirubin is one of the components in the Chinese medicinal herbs Isatis indigotica and Strobilanthes cusia with immunomodulatory activity on the expression of
RANTES.