Aromadendrin Inhibits T Cell Activation via Regulation of Calcium Influx and NFAT Activity

Molecules. 2020 Oct 8;25(19):4590. doi: 10.3390/molecules25194590.

Abstract

The objective of this study was to assess the inhibitory effect of the flavonoid aromadendrin on T cell activity to identify a non-cytotoxic immunosuppressive reagent. Conventional and qualitative PCR, MTT assays, flow cytometry and Western blotting were used to evaluate the effect of aromadendrin on the activity, cell viability and confluency, and proximal signal transduction of activated T cells. Aromadendrin effectively regulated IL-2 and IFNγ production in vitro from activated Jurkat T cells without cytotoxicity. Pre-treatment with aromadendrin also suppressed the expression levels of surface molecules CD69, CD25, and CD40L. Reduced calcium (Ca2+) influx in activated T cells pre-treated with aromadendrin was observed. Western blotting revealed that aromadendrin blocked the dephosphorylation of nuclear factor of activated T (NFAT) cells and its nuclear translocation. Involvement of the NFκB and MAPK pathways in the inhibitory effect of aromadendrin was also demonstrated. Results obtained demonstrated the suppressive effect of aromadendrin on T cell activation by Ca2+ influx regulation through NFAT activity suppression of the activated T cells.

Keywords: IL-2; MAPK; NFAT; T cells; calcium.

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD40 Ligand / metabolism
  • Calcium / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Flavonoids / pharmacology*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Jurkat Cells
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation / drug effects*
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism*
  • Signal Transduction / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Flavonoids
  • Immunosuppressive Agents
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • NF-kappa B
  • NFATC Transcription Factors
  • CD40 Ligand
  • aromadedrin
  • Mitogen-Activated Protein Kinases
  • Calcium