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Biochem Biophys Res Commun. 2005 Dec 30;338(4):1719-25. Epub 2005 Nov 7.

Negatively charged phospholipids suppress IFN-gamma production in T cells.

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School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.


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.

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