| pubmed-article:21036898 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C0003392 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C0011306 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C0282554 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C0079189 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C1411976 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C0023688 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C0054173 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C1551336 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:21036898 | lifeskim:mentions | umls-concept:C1710548 | lld:lifeskim |
| pubmed-article:21036898 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:21036898 | pubmed:dateCreated | 2011-1-3 | lld:pubmed |
| pubmed-article:21036898 | pubmed:abstractText | Bryostatin-1 (Bryo-1), a natural macrocyclic lactone, is clinically used as an anti-cancer agent. In this study, we demonstrate for the first time that Bryo-1 acts as a Toll-like receptor 4 (TLR4) ligand. Interestingly, activation of bone marrow-derived dendritic cells (in vitro with Bryo-1) led to a TLR4-dependent biphasic activation of nuclear factor-?B (NF-?B) and the unique induction of cytokines (IL-5, IL-6, and IL-10) and chemokines, including RANTES (regulated on activation normal T cell expressed and secreted) and macrophage inflammatory protein 1? (MIP1-?). In addition, EMSA demonstrated that Bryo-1-mediated induction of RANTES was regulated by NF-?B and the interferon regulatory factors (IRF)-1, IRF-3, and IRF-7 to the RANTES independently of myeloid differentiation primary response gene-88 (MyD88). Bryo-1 was able to induce the transcriptional activation of IRF-3 through the TLR4/MD2-dependent pathway. In vivo administration of Bryo-1 triggered a TLR-4-dependent T helper cell 2 (Th2) cytokine response and expanded a subset of myeloid dendritic cells that expressed a CD11c(high)CD8?(-) CD11b(+)CD4(+) phenotype. This study demonstrates that Bryo-1 can act as a TLR4 ligand and activate innate immunity. Moreover, the ability of Bryo-1 to trigger RANTES and MIP1-? suggests that Bryo-1 could potentially be used to prevent HIV-1 infection. Finally, induction of a Th2 response by Bryo-1 may help treat inflammatory diseases mediated by Th1 cells. Together, our studies have a major impact on the clinical use of Bryo-1 as an anti-cancer and immunopotentiating agent. | lld:pubmed |
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| pubmed-article:21036898 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21036898 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21036898 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21036898 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21036898 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21036898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21036898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21036898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21036898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21036898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21036898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21036898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21036898 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21036898 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:21036898 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:21036898 | pubmed:author | pubmed-author:NagarkattiPra... | lld:pubmed |
| pubmed-article:21036898 | pubmed:author | pubmed-author:NagarkattiMit... | lld:pubmed |
| pubmed-article:21036898 | pubmed:author | pubmed-author:ArizaMaria... | lld:pubmed |
| pubmed-article:21036898 | pubmed:author | pubmed-author:SinghNarendra... | lld:pubmed |
| pubmed-article:21036898 | pubmed:author | pubmed-author:ChauhanAshokA | lld:pubmed |
| pubmed-article:21036898 | pubmed:author | pubmed-author:RamakrishnanR... | lld:pubmed |
| pubmed-article:21036898 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21036898 | pubmed:day | 7 | lld:pubmed |
| pubmed-article:21036898 | pubmed:volume | 286 | lld:pubmed |
| pubmed-article:21036898 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21036898 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21036898 | pubmed:pagination | 24-34 | lld:pubmed |
| pubmed-article:21036898 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:21036898 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21036898 | pubmed:articleTitle | Bryostatin-1, a naturally occurring antineoplastic agent, acts as a Toll-like receptor 4 (TLR-4) ligand and induces unique cytokines and chemokines in dendritic cells. | lld:pubmed |
| pubmed-article:21036898 | pubmed:affiliation | Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29208, USA. | lld:pubmed |
| pubmed-article:21036898 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21036898 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
