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

• Published in: Biological & pharmaceutical bulletin 2010/01/01, Vol.33(1), pp.40-46
• Main Authors: Li, Ting, Wong, Vincent Kam Wai, Yi, Xiao Qin, Wong, Yuen Fan, Zhou, Hua, Liu, Liang
• Format: Article
• Language: English
• Subjects: Alkaloids - pharmacology; Antigens - genetics; Antigens - metabolism; Autoimmune Diseases - drug therapy; Autoimmune Diseases - genetics; cell anergy; Clonal Anergy - drug effects; Clonal Anergy - genetics; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; herbal medicine; Humans; immunotolerance inducer; Interleukin-2 - genetics; Interleukin-2 - metabolism; Ionomycin; Ionophores; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; Jurkat Cells; Jurkat T cell; matrine; Mitogen-Activated Protein Kinases - metabolism; Muromonab-CD3; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; Phytotherapy; Plant Extracts - pharmacology; Plant Roots; Quinolizines - pharmacology; RNA, Messenger - metabolism; Signal Transduction - drug effects; Signal Transduction - genetics; Signal Transduction - immunology; Sophora; Sophora - chemistry; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Transcription Factor AP-1; Up-Regulation
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.33.40

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.