Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation

Eur J Pharmacol. 2009 Jan 14;602(2-3):413-21. doi: 10.1016/j.ejphar.2008.11.011. Epub 2008 Nov 13.


The nuclear factor of activated T cells (NFAT) is a transcription factor essential for cytokine production during T-cell activation and is the target of several immunosuppressive drugs. Andrographolide is a diterpenic labdane that possesses anti-inflammatory and immunomodulatory effects. Several studies propose that andrographolide can reduce the immune response through inhibition of the nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinases (MAPK) such as extracellular signal regulated kinase 1/2 (ERK1/2) pathways. Moreover, andrographolide reduces IFN-gamma and IL-2 production induced by concanavalin A in murine T-cell. Nevertheless, the mechanisms involved in the decrease of cytokine production are unknown. In the present study, we determined that andrographolide reduced IL-2 production in Jurkat cells stimulated with phorbol myristate acetate and ionomycin (PMA/Ionomycin). We then showed that andrographolide reduced NFAT luciferase activity and interfered with its nuclear distribution, with these effects being linked to an increase in c-jun-N-terminal kinase (JNK) phosphorylation. Additionally, reduction of NF-kappaB activity in Jurkat cells treated with andrographolide was observed. Using Western blotting, we demonstrated that andrographolide decreased ERK1 and ERK5 phosphorylation induced by anti-CD3 or PMA/Ionomycin. Andrographolide did not affect cell viability at concentration of 10 and 50 muM; however, our results suggest that andrographolide increase early apoptosis at 100 muM. We concluded that andrographolide can exert immunomodulatory effects by interfering with NFAT activation and ERK1 and ERK5 phosphorylation in T-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • CD3 Complex / immunology
  • Calcium / metabolism
  • Cell Survival / drug effects
  • Diterpenes / pharmacology*
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Interleukin-2 / biosynthesis*
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Ionomycin / pharmacology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Jurkat Cells
  • Luciferases / metabolism
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • NFATC Transcription Factors / metabolism*
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology


  • Antibodies, Monoclonal
  • CD3 Complex
  • Diterpenes
  • Interleukin-2
  • NFATC Transcription Factors
  • andrographolide
  • Ionomycin
  • Luciferases
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Tetradecanoylphorbol Acetate
  • Calcium