title: Magnesium lithospermate B mediates anti-inflammation targeting activator protein-1 and nuclear factor-kappa B signaling pathways in human peripheral T lymphocytes.
abstract: The activation of T lymphocytes contributes to the inflammatory processes of atherosclerotic diseases. Danshen is a traditional Chinese medicine and has shown therapeutic effects in patients with cardiovascular and cerebrovascular diseases. We investigated the effects of aqueous extract of Danshen (magnesium lithospermate B (MLB)) on phorbol 12-myristate acetate+ionomycin and anti-CD3+anti-CD28 monoclonal antibody-activated T cells. We showed that MLB inhibited interleukin (IL)-2, IL-4, tumor necrosis factor-alpha and interferon-gamma production from activated T cells. The expressions of T cell activation markers CD 25 and CD 69 were effectively reduced. EMSA analysis indicated that MLB down-regulated activator protein-1 (AP-1), nuclear factor kappa B (NF-κB) and octamer binding transcription factor (Oct-1) DNA-binding activity. In addition, MLB inhibited c-jun N-terminal kinase (JNK) but not extracellular signal regulated protein kinase activity. MLB also inhibited IκBα degradation, nuclear translocation of p65 and p50 as well as decreased IκBα kinase (IKK) activity. Through suppressing JNK-AP-1, IKK-IκBα-NF-κB and Oct-1 signaling pathways by MLB in activated T cells, our results provide support for efficacy of MLB in inflammatory diseases and raise its therapeutic potential in activated T cell-mediated pathologies.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325 Section 2 Cheng-Kung Road, Neihu, Taipei, Taiwan, ROC.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Cheng
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Yang
authors.forename: Wei-Shiang
authors.initials: WS
authors.lastname: Lin
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Ho
authors.forename: Jenn-Haung
authors.initials: JH
authors.lastname: Lai
authors.forename: Shu-Meng
authors.initials: SM
authors.lastname: Cheng
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Lin
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D050811:Octamer Transcription Factor-1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D050811:Octamer Transcription Factor-1; D018808:Transcription Factor AP-1; C061091:lithospermate B; D004247:DNA