Negatively charged phospholipids suppress IFN-gamma production in T cells.
The effect of phospholipids on IFN-gamma production in mouse T cells was investigated. Phosphatidylserine (PS), which has a negatively charged head group, completely inhibited IFN-gamma production in splenic naïve T cells and antigen-dependent IFN-gamma production in Th1 clone 42-6A cells, whereas other phospholipids, which have neutrally charged head group, had no effect. The structural requirements for IFN-gamma inhibitory effects by PS were investigated, and dimyristoyl-PS (C14: 0) and dipalmitoyl-PS (C16: 0) had no effect on IFN-gamma production, and interestingly, distearoyl-PS (18: 0) increased IFN-gamma production. Dioleoyl-PS (C18: 1), dilinoleoyl-PS (C18: 2), and oleoyl-lyso-PS (C18: 1) completely inhibited IFN-gamma production. To clarify this mechanism, we focused on the stability of IFN-gamma mRNA, and the treatment of splenic naïve T cells with PS brought about 40% reductions in IFN-gamma mRNA expression in the presence of actinomycin D. Collectively, IFN-gamma inhibitory effects by PS are highly dependent on the molecular structure of PS and involve the decreasing of the stability of IFN-gamma mRNA.
Yotsumoto
Satoshi
S
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Kakiuchi
Terutaka
T
Aramaki
Yukihiko
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010718:Phosphatidylserines / Q000494:pharmacology*; D010743:Phospholipids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D010718:Phosphatidylserines; D010743:Phospholipids; D012333:RNA, Messenger; D003208:Concanavalin A; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate