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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-5-11
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pubmed:abstractText |
G1-4A, a polysaccharide from an Indian medicinal plant Tinospora cordifolia, was recently shown to protect mice against septic shock by modulating the proinflammatory cytokines. G1-4A also activated B cells polyclonally. The present report describes in detail the molecular events associated with G1-4A-induced immunomodulation in vitro and in vivo. G1-4A treatment led to an increase in the CD69 expression in lymphocytes. G1-4A-induced proliferation of B cells was completely inhibited by PI3K inhibitor Ly294002, mTOR inhibitor rapamycin and NF-kappaB inhibitor plumbagin. Akt, ERK and JNK were activated by G1-4A which finally resulted in the activation of IKK, degradation of IkappaB-alpha and translocation of NF-kappaB to the nucleus. Administration of G1-4A to mice led to splenomegaly and an increase in the numbers of T cells, B cells and macrophages. This increase in spleen cellularity was due to in vivo proliferation of lymphocytes and upregulation of anti-apoptotic genes. Anti-TLR4-MD2 complex antibody inhibited G1-4A-induced B cell proliferation and degradation of IkappaB-alpha suggesting that TLR-4 was a receptor for G1-4A on B cells. Activation of RAW 264.7 macrophages by G1-4A was found to be dependent on ERK and NF-kappaB-mediated signals. The phagocytosis index in peritoneal exudate cells (PEC) isolated from G1-4A treated mice was significantly higher as compared to that in PEC from control mice. G1-4A administration also increased the number of CD11b(+) cells in the PEC without an increase in the total number of PEC. Thus the present understanding of the molecular mechanism of action of G1-4A, a novel non-microbial TLR4 agonist, will pave the way for its application as an immunomodulator and adjuvant.
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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/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/CD69 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Polysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/plumbagin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1879-0542
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
123
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
60-71
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19428553-Adjuvants, Immunologic,
pubmed-meshheading:19428553-Animals,
pubmed-meshheading:19428553-Antigens, CD,
pubmed-meshheading:19428553-Antigens, Differentiation, T-Lymphocyte,
pubmed-meshheading:19428553-B-Lymphocytes,
pubmed-meshheading:19428553-Carrier Proteins,
pubmed-meshheading:19428553-Cell Line,
pubmed-meshheading:19428553-Cell Proliferation,
pubmed-meshheading:19428553-Chromones,
pubmed-meshheading:19428553-Enzyme Inhibitors,
pubmed-meshheading:19428553-Flavonoids,
pubmed-meshheading:19428553-Lectins, C-Type,
pubmed-meshheading:19428553-Lymphocyte Activation,
pubmed-meshheading:19428553-MAP Kinase Kinase Kinases,
pubmed-meshheading:19428553-Macrophages,
pubmed-meshheading:19428553-Mice,
pubmed-meshheading:19428553-Morpholines,
pubmed-meshheading:19428553-NF-kappa B,
pubmed-meshheading:19428553-Naphthoquinones,
pubmed-meshheading:19428553-Phagocytosis,
pubmed-meshheading:19428553-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19428553-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:19428553-Polysaccharides,
pubmed-meshheading:19428553-Protein Kinases,
pubmed-meshheading:19428553-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:19428553-Sirolimus,
pubmed-meshheading:19428553-Splenomegaly,
pubmed-meshheading:19428553-TOR Serine-Threonine Kinases,
pubmed-meshheading:19428553-Tinospora,
pubmed-meshheading:19428553-Toll-Like Receptor 4
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pubmed:year |
2009
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pubmed:articleTitle |
Molecular events in the activation of B cells and macrophages by a non-microbial TLR4 agonist, G1-4A from Tinospora cordifolia.
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pubmed:affiliation |
Radiation Biology & Health Sciences Division, Bio-Medical Group, Bhabha Atomic Research Centre, Modular Laboratories, Trombay, Mumbai 400085, India.
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pubmed:publicationType |
Journal Article
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