title: 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.
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 NH(2)-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.
authors.affiliation: Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Vincent Kam Wai
authors.initials: VK
authors.lastname: Wong
authors.forename: Xiao Qin
authors.initials: XQ
authors.lastname: Yi
authors.forename: Yuen Fan
authors.initials: YF
authors.lastname: Wong
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics; D017635:Clonal Anergy / Q000187:drug effects* / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015759:Ionomycin; D007476:Ionophores; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016853:Muromonab-CD3; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots; D011807:Quinolizines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D029909:Sophora / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018808:Transcription Factor AP-1; D015854:Up-Regulation; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000941:Antigens; D007376:Interleukin-2; D007476:Ionophores; D016853:Muromonab-CD3; D050778:NFATC Transcription Factors; D010936:Plant Extracts; D011807:Quinolizines; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D015759:Ionomycin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D000093842:Matrines