Get access

Interleukin-1β-induced interleukin-6 production in A549 cells is mediated by both phosphatidylinositol 3-kinase and interleukin-1 receptor-associated kinase-4

Authors

  • Hiroyuki Eda,

    Corresponding author
    1. Discovery Biology, Global Research and Development, St. Louis Laboratories Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, U.S.A.
    Search for more papers by this author
  • Barry L. Burnette,

    1. Discovery Biology, Global Research and Development, St. Louis Laboratories Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, U.S.A.
    Search for more papers by this author
  • Hideaki Shimada,

    1. Discovery Biology, Global Research and Development, St. Louis Laboratories Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, U.S.A.
    Search for more papers by this author
  • Heidi R. Hope,

    1. Discovery Biology, Global Research and Development, St. Louis Laboratories Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, U.S.A.
    Search for more papers by this author
  • Joseph B. Monahan

    1. Discovery Biology, Global Research and Development, St. Louis Laboratories Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, U.S.A.
    Search for more papers by this author

To whom correspondence should be addressed (email hiroyuki_eda@ajinomoto.com).

Exploratory Research Laboratories, Research Center, Ajinomoto Pharmaceuticals Co., Ltd., 1-1, Suzuki, Kawasaki, Kanagawa, 210-8681, Japan

Abstract

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.

Ancillary