The aim of this study is to investigate whether PI3K (phosphatidylinositol-3-kinase) is involved in IL-1β (interleukin-1β)-induced
IL-6 production in A549 (human
lung adenocarcinoma epithelial cell) and human RASF (
rheumatoid arthritis synovial fibroblast). PI3K inhibitor,
LY294002 significantly reduced IL-1β-induced
IL-6 production in A549 cells but not in RASF, indicating that IL-1β-induced
IL-6 production was partially mediated by PI3Kin A549 cells but not in RASF.
siRNA (
small interfering RNA) of IRAK4 (
IL-1 receptor-associated kinase 4) treatment decreased IRAK4
mRNA level by up to 90% in A549 cells. In this condition, IL-1β-induced increase of
IL-6 mRNA and
protein level was decreased by up to 93% and 70%, respectively. Furthermore, the combination of IRAK4
siRNA and
LY294002 treatment decreased
protein induction level of
IL-6 in A549 cells compared with that of IRAK4
siRNA or
LY294002 alone. These results indicate that IL-1β-induced
IL-6 production in A549 cells is mediated by both PI3K and IRAK4 and suggest that involvement of PI3K in the IL-1-induced
IL-6 production is cell type specific.