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


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 NFkappaB (nuclear factor kappa B), which are transcription factors required for CIIP.


RESULTS
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 NFkappaB. Unlike cyclosporine A and FK506, the DIF derivatives had little effect on concanavalin A-induced interferon-gamma production in Jurkat cells.


CONCLUSIONS
The present results suggest that DIF derivatives could be developed as novel immunosuppressive drugs.
Takahashi
Katsunori
K
Department of Clinical Laboratory, Gunma University School of Medicine, Maebashi 371-8511, Japan.
Murakami
Masami
M
Hosaka
Kohei
K
Kikuchi
Haruhisa
H
Oshima
Yoshiteru
Y
Kubohara
Yuzuru
Y
D041721:3T3-L1 Cells; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004023:Dictyostelium / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D020014:K562 Cells; D008156:Luciferases / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000502:physiology
D007202:Indicators and Reagents; D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D018808:Transcription Factor AP-1; D003208:Concanavalin A; D007371:Interferon-gamma; D008156:Luciferases; D005947:Glucose