Ursolic acid inhibits T-cell activation through modulating nuclear factor-κ B signaling

Chin J Integr Med. 2012 Jan;18(1):34-9. doi: 10.1007/s11655-011-0858-0. Epub 2011 Oct 12.

Abstract

Objective: To investigate the effects of ursolic acid (UA) on T-cell proliferation and activation, as well as to examine its effect on nuclear factor-κB (NF-κB) signaling pathway in T cells.

Methods: T-cells isolated from BALB/c mice were incubated with UA at concentrations ranging from 5-30 μmol/L in the presence of phorbol 12-myristate 13-acetate (PMA) or PMA plus ionomycin. The proliferation of T cells was measured by the MTT assay. The expressions of CD69, CD25, and CD71 on T-cell surface were analyzed using flow cytometry. The level of interleukin-2 (IL-2) in the culture supernatant of activated T cells was quantified by enzyme-linked immunosorbent assay (ELISA). The level of phosphorylated IκB-α (p-IκB-α) in total protein and p65, a subunit of NF-κB, nuclear translocation were measured by Western blot analysis.

Results: UA in a dose-dependent manner significantly decreased the proliferation and inhibited the surface expressions of CD69, CD25, and CD71 in murine T lymphocytes upon in vitro activation (P<0.01). Significant reduction of IL-2 production was found in activated T cells treated with UA (P<0.01). The PMA-induced increase in p-IκB-α protein was inhibited, and nuclear translocation of p65 from the cytoplasm was blocked by UA.

Conclusion: UA is a potent inhibitor for T cell activation and proliferation; these effects are associated with the inhibition of NF-κB signaling pathway.

MeSH terms

  • Animals
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • I-kappa B Proteins / metabolism
  • Interleukin-2 / metabolism
  • Ionomycin / pharmacology
  • Lymphocyte Activation / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Signal Transduction / drug effects*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Triterpenes / pharmacology*
  • Ursolic Acid

Substances

  • I-kappa B Proteins
  • Interleukin-2
  • NF-kappa B
  • Nfkbia protein, mouse
  • Triterpenes
  • NF-KappaB Inhibitor alpha
  • Ionomycin
  • Tetradecanoylphorbol Acetate