Tetradecanol reduces EL-4 T cell growth by the down regulation of NF-κB mediated IL-2 secretion

Eur J Pharmacol. 2017 Mar 15:799:135-142. doi: 10.1016/j.ejphar.2017.02.002. Epub 2017 Feb 3.

Abstract

Tetradecanol is a straight-chain saturated fatty alcohol purified from Dendropanax morbifera leaves. We found that tetradecanol (30μM) reduced specifically the growth of T cells such as EL-4 T cell and isolated murine CD4+ T cells. In this study, we investigated the effects of tetradecanol on the regulation of interlukin-2 (IL-2), a potent T cell growth factor. Tetradecanol significantly inhibited IL-2 secretion in EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io) and also in isolated murine CD4+ T cells activated with anti-CD3 and anti-CD28 antibodies. Next, we examined the effect of tetradecanol on the transcriptional activity related to IL-2 production in T cells. Tetradecanol decreased PMA/Io-induced promoter activity of NF-κB in EL-4 T cells, but did not show any significant effects on the promoters of activator protein 1 (AP-1) and nuclear factor of activated T cells (NF-AT). Tetradecanol inhibited IκBα degradation and nuclear translocation of NF-κB subunit, p65 in PMA/Io-activated EL-4 T cells. These results suggest that tetradecanol might have immunosuppressive effects on T cell mediated disorders. Using a chronic allergic contact dermatitis model induced by repeated application of oxazolone, we showed that tetradecanol reduced ear thickness induced by oxazolone.

Keywords: Contact dermatitis; IL-2; NF-κB; T cell; Tetradecanol.

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dermatitis, Contact / complications
  • Dermatitis, Contact / drug therapy
  • Down-Regulation / drug effects*
  • Fatty Alcohols / pharmacology*
  • Fatty Alcohols / therapeutic use
  • Female
  • HeLa Cells
  • Humans
  • Hypersensitivity / complications
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism*
  • Male
  • Mice
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism*
  • Proteolysis / drug effects
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Transcription, Genetic / drug effects

Substances

  • Fatty Alcohols
  • Interleukin-2
  • NF-kappa B
  • NF-KappaB Inhibitor alpha