Negatively charged phospholipids suppress IFN-gamma production in T cells

Biochem Biophys Res Commun. 2005 Dec 30;338(4):1719-25. doi: 10.1016/j.bbrc.2005.10.179. Epub 2005 Nov 7.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD3 Complex / immunology
  • Concanavalin A / pharmacology
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / biosynthesis*
  • Ionomycin / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Phosphatidylserines / pharmacology*
  • Phospholipids / pharmacology*
  • RNA, Messenger / metabolism
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Th1 Cells / drug effects

Substances

  • Antibodies, Monoclonal
  • CD3 Complex
  • Phosphatidylserines
  • Phospholipids
  • RNA, Messenger
  • Concanavalin A
  • Ionomycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate