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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2007-5-3
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pubmed:abstractText |
Chinese herbs are useful edible and medicinal plants for their immune modulatory functions. We have proven that (S)-armepavine (C19H23O3N; MW313) from Nelumbo nucifera inhibits the proliferation of human PBMCs activated with PHA and improves autoimmune diseases in MRL/MpJ-lpr/lpr mice. In the present study, the pharmacological activities of (S)-armepavine were evaluated in PHA-activated PBMCs. The results showed that (S)-armepavine suppressed PHA-induced PBMC proliferation and genes expression of IL-2 and IFN-gamma without direct cytotoxicity. Inhibition of NF-AT and NF-kappaB activation suggested phospholipase Cgamma (PLCgamma)-mediated Ca2+ mobilization and protein kinase C activation were blocked by (S)-armepavine. Phosphorylation of PLCgamma is regulated by lymphocyte-specific kinase (Lck), ZAP-70, and IL-2-inducible T cell kinase (Itk). We found (S)-armepavine inhibited PHA-induced phosphorylation of Itk and PLCgamma efficiently but did not influence Lck or ZAP-70 phosphorylation. In addition, ZAP-70-mediated pathways, such as the association of linker for activation of T cells with PLCgamma and activation of ERK, were also intact in the presence of (S)-armepavine. Finally, reduction of phosphoinositide 3,4,5-trisphosphate formation and Akt phosphorylation suggested that (S)-armepavine inhibited Itk, and PLCgamma phosphorylation might be a result of the influence of PI-3K activation. Addition of exogenous IL-2 or PMA/A23187 rescued PBMC proliferation in the presence of (S)-armepavine. Therefore, we concluded that (S)-armepavine inhibited PHA-induced cell proliferation and cytokine production in a major way by blocking membrane-proximal effectors such as Itk and PLCgamma in a PI-3K-dependent manner.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Benzylisoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/armepavine,
http://linkedlifedata.com/resource/pubmed/chemical/emt protein-tyrosine kinase
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0741-5400
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1276-86
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17284681-Alkaloids,
pubmed-meshheading:17284681-Benzylisoquinolines,
pubmed-meshheading:17284681-Calcimycin,
pubmed-meshheading:17284681-Calcium,
pubmed-meshheading:17284681-Cell Proliferation,
pubmed-meshheading:17284681-Dose-Response Relationship, Drug,
pubmed-meshheading:17284681-Humans,
pubmed-meshheading:17284681-Interferon-gamma,
pubmed-meshheading:17284681-Interleukin-2,
pubmed-meshheading:17284681-Leukocytes, Mononuclear,
pubmed-meshheading:17284681-Molecular Conformation,
pubmed-meshheading:17284681-Molecular Weight,
pubmed-meshheading:17284681-NF-kappa B,
pubmed-meshheading:17284681-NFATC Transcription Factors,
pubmed-meshheading:17284681-Nelumbo,
pubmed-meshheading:17284681-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17284681-Phospholipase C gamma,
pubmed-meshheading:17284681-Phosphorylation,
pubmed-meshheading:17284681-Protein Kinase C,
pubmed-meshheading:17284681-Protein-Tyrosine Kinases,
pubmed-meshheading:17284681-RNA, Messenger,
pubmed-meshheading:17284681-Seeds,
pubmed-meshheading:17284681-Structure-Activity Relationship,
pubmed-meshheading:17284681-Tetradecanoylphorbol Acetate
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pubmed:year |
2007
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pubmed:articleTitle |
(S)-armepavine inhibits human peripheral blood mononuclear cell activation by regulating Itk and PLCgamma activation in a PI-3K-dependent manner.
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pubmed:affiliation |
Institute of Pharmacology, National Yang-Ming University, Laboratory of Biochemistry, National Research Institute of Chinese Medicine, No. 155-1, Sec. 2, Li-Nung St., Shih-Pai, 112, Taipei, Taiwan, ROC.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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