Matrine induces cell anergy in human jurkat T cells through modulation of mitogen-activated protein kinases and nuclear factor of activated t-cells signaling with concomitant up-regulation of anergy-associated genes expression

Ting Li, Vincent Kam Wai Wong, Xiao Qin Yi, Yuen Fan Wong, Hua Zhou, Liang LIU*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Induction of immunotolerance has become a new strategy for treating autoimmune conditions in recent decades. However, so far there is no ideal therapeutics available for clinical use. Medicinal herbs are a promising potential source of immunotolerance inducers. In the current study, we sought first to optimize conditions for a validated cellular model of human Jurkat cells; and then used this model to screen bioactive compounds derived from medicinal plants for inducing T cell anergy in comparison with the effect of well-known T cell anergy inducer, ionomycin. The results showed that passage of the cells, and concentration and stimulation time of ionomycin on the cells could influence the ability of T cell anergy induction. Matrine, a small molecule derived from the root of Sophora flavescens AIT., was demonstrated to be effective in inducing T cell anergy in human Jurkat cells. The cells exposed to matrine showed markedly decreased mRNA expression of interleukin-2, an indicator of T cell anergy, when the cells were stimulated by antigens, anti-OKT3 plus anti-CD28. Mechanistic study showed that ionomycin and matrine could up-regulate the anergy-associated gene expressions of CD98 and Jumonji and activate nuclear factor of activated T-cells (NFAT) nuclear translocation in absence of cooperation of AP-1 in Jurkat cells. Pre-incubation with matrine or ionomycin could also shorten extracellular signal-regulated kinase (ERK) and suppress c-Jun NH2-terminal kinase (JNK) expression on the anergic Jurkat cells when the cells were stimulated with anti-OKT-3 plus anti-CD28 antibodies. Thus, matrine is a strong candidate for further investigation as a T cell immunotolerance inducer.

Original languageEnglish
Pages (from-to)40-46
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 2010

Scopus Subject Areas

  • Pharmacology
  • Pharmaceutical Science

User-Defined Keywords

  • Cell anergy
  • Herbal medicine
  • Immunotolerance inducer
  • Jurkat T cell
  • Matrine

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