Regulation of IL-2 production in Jurkat cells by Dictyostelium

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• 作者：Katsunori Takahashi ; Masami Murakami ; Kohei Hosaka ; Haruhisa Kikuchi ; Yoshiteru Oshima ; Yuzuru Kubohara
• 关键词：Dictyostelium ; Differentiation-inducing factor ; DIF ; Interleukin-2 ; Interferon-γ ; Immunosuppressive drug ; Jurkat cells
• 刊名：Life Sciences
• 出版年：2009
• 出版时间：9 September 2009
• 年：2009
• 卷：85
• 期：11-12
• 页码：438-443
• 全文大小：563 K

文摘

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.