| pubmed-article:15184382 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15184382 | lifeskim:mentions | umls-concept:C0028953 | lld:lifeskim |
| pubmed-article:15184382 | lifeskim:mentions | umls-concept:C0963057 | lld:lifeskim |
| pubmed-article:15184382 | lifeskim:mentions | umls-concept:C0332621 | lld:lifeskim |
| pubmed-article:15184382 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:15184382 | pubmed:issue | 32 | lld:pubmed |
| pubmed-article:15184382 | pubmed:dateCreated | 2004-8-2 | lld:pubmed |
| pubmed-article:15184382 | pubmed:abstractText | Toll-like receptor 9 (TLR9), a member of the interleukin-1 (IL-1) family of pathogen-associated molecular pattern receptors, is activated by unmethylated CpG-containing sequences in bacterial DNA or synthetic oligonucleotides (ODNs) in the endosomal compartment. The stimulation of an IL-1 response is thought to require the aggregation of its receptor. By analogy, we postulated that the potency of a TLR9 ligand should depend first on its ability to enter cells and gain access to TLR9 and second on its capacity to form a multimeric complex capable of cross-linking these receptors. Previously, we selected from a random library a series of phosphodiester ODNs with enhanced ability to permeate cells. Here, we studied the structural requirements for these penetrating ODNs to elicit a functional TLR9 response, as assessed by cytokine production from bone marrow-derived mouse mononuclear cells. The presence of a prototypic murine immunostimulatory DNA hexameric sequence (purine-purine-CG-pyrimidine-pyrimidine) in the ODNs was not sufficient for stimulation. In addition, the TLR9-activating ODNs had to have the ability to form aggregates and often to form secondary structures near the core CpG motifs. Multimerization was promoted by the presence of a guanine-rich 3'-terminus. The phosphodiester ODNs with CpG motifs that did not aggregate antagonized the effects of the multimeric TLR9 activators. These findings suggest that an optimal TLR9 agonist needs to contain a spatially distinct multimerization domain and a receptor binding CpG domain. This concept may prove useful for the design of new TLR9-modulating agents. | lld:pubmed |
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| pubmed-article:15184382 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15184382 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15184382 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15184382 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15184382 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15184382 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15184382 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:15184382 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15184382 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15184382 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:15184382 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:15184382 | pubmed:author | pubmed-author:FiegE LEL | lld:pubmed |
| pubmed-article:15184382 | pubmed:author | pubmed-author:CarsonDennis... | lld:pubmed |
| pubmed-article:15184382 | pubmed:author | pubmed-author:CorrMaripatM | lld:pubmed |
| pubmed-article:15184382 | pubmed:author | pubmed-author:LeeJongdaeJ | lld:pubmed |
| pubmed-article:15184382 | pubmed:author | pubmed-author:WuChristina... | lld:pubmed |
| pubmed-article:15184382 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15184382 | pubmed:day | 6 | lld:pubmed |
| pubmed-article:15184382 | pubmed:volume | 279 | lld:pubmed |
| pubmed-article:15184382 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15184382 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15184382 | pubmed:pagination | 33071-8 | lld:pubmed |
| pubmed-article:15184382 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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| pubmed-article:15184382 | pubmed:meshHeading | pubmed-meshheading:15184382... | lld:pubmed |
| pubmed-article:15184382 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15184382 | pubmed:articleTitle | Necessity of oligonucleotide aggregation for toll-like receptor 9 activation. | lld:pubmed |
| pubmed-article:15184382 | pubmed:affiliation | Division of Rheumatology Allergy and Immunology, Department of Medicine and the Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, California 92093-0663, USA. c5wu@ucsd.edu | lld:pubmed |
| pubmed-article:15184382 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15184382 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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