Derivatives of Dictyostelium differentiation-inducing factors promote mitogen-activated IL-2 production via AP-1 in Jurkat cells

Aims: Differentiation-inducing factors (DIFs) are chlorinated alkylphenones found in the cellular slime mold Dictyostelium discoideum. DIF derivatives exhibit antiproliferative activities and promote glucose consumption in mammalian cells in vitro. Here, we assessed the ability of DIFs to regulate the immune system in a mammalian cell-line and investigated their mechanisms of action. Main methods: We examined the effects of 30 DIF derivatives on concanavalin A-induced interleukin-2 (IL-2) production (CIIP) in Jurkat T-cells. We also examined the effects of these DIF derivatives on the activity of three transcription factors required for CIIP: namely, activator protein-1 (AP-1), nuclear factor of activated T-cells (NFAT), and nuclear factor kappa B (NFκB). Key findings: A reporter gene assay suggested that 2 DIF derivatives, termed DIF-1(+ 1) and DIF-3(3 M), significantly promoted CIIP in Jurkat cells, at least in part, by enhancing the activity of AP-1. These 2 DIF derivatives had no significant effect on concanavalin A-induced interferon-γ production. Significance: The results suggest that DIF derivatives could be developed as novel drugs for the activation of IL-2 production and resultant stimulation of the immune system.