Regulation of IL-2 production in Jurkat cells by Dictyostelium-derived factors

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

Research output: Contribution to journalArticle

18 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. In this study, we assessed the ability of DIFs to regulate the immune system and investigated their mechanisms of action. Main methods: We examined the effects of 30 DIF derivatives on concanavalin A-induced IL-2 production (CIIP) in Jurkat T-cells. We also examined the effects of some DIF derivatives on the activity of AP-1 (activator protein-1), NFAT (nuclear factor of activated T-cells), and NFκB (nuclear factor kappa B), which are transcription factors required for CIIP. Key findings: Of the derivatives tested, some compounds suppressed CIIP as well as the known immunosuppressants cyclosporine A and FK506. A reporter gene assay revealed that 4 DIF derivatives tested suppressed CIIP, at least in part, by inhibiting the activity of AP-1, NFAT, and/or NFκB. Unlike cyclosporine A and FK506, the DIF derivatives had little effect on concanavalin A-induced interferon-γ production in Jurkat cells. Significance: The present results suggest that DIF derivatives could be developed as novel immunosuppressive drugs.

Original languageEnglish
Pages (from-to)438-443
Number of pages6
JournalLife Sciences
Volume85
Issue number11-12
DOIs
Publication statusPublished - 2009 Sep 9

Keywords

  • DIF
  • Dictyostelium
  • Differentiation-inducing factor
  • Immunosuppressive drug
  • Interferon-γ
  • Interleukin-2
  • Jurkat cells

ASJC Scopus subject areas

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

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  • Cite this

    Takahashi, K., Murakami, M., Hosaka, K., Kikuchi, H., Oshima, Y., & Kubohara, Y. (2009). Regulation of IL-2 production in Jurkat cells by Dictyostelium-derived factors. Life Sciences, 85(11-12), 438-443. https://doi.org/10.1016/j.lfs.2009.07.008