title: Interleukin-1β-induced interleukin-6 production in A549 cells is mediated by both phosphatidylinositol 3-kinase and interleukin-1 receptor-associated kinase-4.
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.
authors.affiliation: Discovery Biology, Global Research and Development, St. Louis Laboratories Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA. hiroyuki_eda@ajinomoto.com
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Eda
authors.forename: Barry L
authors.initials: BL
authors.lastname: Burnette
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Hope
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Monahan
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008168:Lung / Q000166:cytology*; D058539:Phosphatidylinositol 3-Kinase / Q000276:immunology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D058539:Phosphatidylinositol 3-Kinase; D053592:Interleukin-1 Receptor-Associated Kinases