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

Katsunori Takahashi, Masami Murakami, Haruhisa Kikuchi, Yoshiteru Oshima, Yuzuru Kubohara

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)480-485
Number of pages6
JournalLife Sciences
Volume88
Issue number11-12
DOIs
Publication statusPublished - 2011 Mar 14
Externally publishedYes

Keywords

  • AP-1
  • Dictyostelium
  • DIF
  • Differentiation-inducing factor
  • Immunomodulatory drug
  • Interferon-γ
  • Interleukin-2
  • Jurkat cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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