We are investigating the mechanism by which flavone-8-acetic acid (FAA) acts to enhance immune responsiveness in murine tumor model systems. Analysis of mRNA isolated from a mouse macrophage cell line after FAA administration indicates that interferon-beta, tumor necrosis factor- alpha, IL-6, MIP-1alpha and interferon response factor-1 mRNA can be detected within three hours. The use of metabolic inhibitors has resulted in the observations that FAA gene induction does not require protein synthesis, involves protein kinase C but not tyrosine kinases and is distinct from the gene induction pathway triggered by LPS. IRF-1 mRNA also appears to be stabilized by the presence of FAA. These results indicate that FAA acts by directly stimulating gene expression of immunoregulatory proteins and establishes a tissue culture model for the molecular elucidation of FAA action.
