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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-7-23
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pubmed:abstractText |
Development of immunomodulatory agents that enhance innate immune responses represents a promising strategy for combating infectious diseases. In the present studies, we screened a series of 71 arylcarboxylic acid hydrazide derivatives for their ability to induce macrophage tumor necrosis factor alpha (TNF-alpha) production and identified six such compounds, including one compound previously shown to be a formyl peptide receptor (FPR/FPRL1) agonist. The two most potent compounds [compound 1, nicotinic acid [5-(3-bromophenyl)-2-furyl]methylene-hydrazide; compound 2, 4-fluoro-benzoic acid [5-(3-trifluoromethyl-phenyl)-2-furyl]-methylene-hydrazide] were selected for further analysis. These compounds induced de novo production of TNF-alpha in a dose- and time-dependent manner in human and murine monocyte/macrophage cell lines and in primary macrophages. These compounds also induced mobilization of intracellular Ca(2+), production of reactive oxygen species, and chemotaxis in human and murine phagocytes. Induction of macrophage TNF-alpha production was pertussis toxin-sensitive, and analysis of the cellular target of these compounds showed that they were FPRL1-specific agonists and that this response was blocked by FPR/FPRL1 and FPRL1-specific antagonists. In addition, pharmacophore modeling showed a high degree of similarity for low-energy conformations of these two compounds to the current pharmacophore model for FPR ligands ( Mol Pharmacol 68: 1301-1310, 2005 ). Overall, these compounds represent novel FPRL1 agonists that induce TNF-alpha, a response distinct from those induced by other known FPR and FPRL1 agonists.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-11063827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-11500829,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-12133977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-12368905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-12560218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-14572803,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-15186849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-15210823,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-15544485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-15829413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-15919931,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-15928303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-15978614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-16551058,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-16755013,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-16826219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-17084101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-17090225,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-17346155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-17575160,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-17972350,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-2021932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-7954398,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-8423328,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-8581425,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-9010769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-9697981,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18458054-9722950
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1521-0111
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
74
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
392-402
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pubmed:dateRevised |
2011-1-7
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pubmed:meshHeading |
pubmed-meshheading:18458054-Animals,
pubmed-meshheading:18458054-Cell Differentiation,
pubmed-meshheading:18458054-Cell Line, Tumor,
pubmed-meshheading:18458054-Cells, Cultured,
pubmed-meshheading:18458054-Dose-Response Relationship, Drug,
pubmed-meshheading:18458054-Humans,
pubmed-meshheading:18458054-Macrophages,
pubmed-meshheading:18458054-Macrophages, Peritoneal,
pubmed-meshheading:18458054-Mice,
pubmed-meshheading:18458054-Mice, Inbred BALB C,
pubmed-meshheading:18458054-Pharmaceutical Preparations,
pubmed-meshheading:18458054-Rats,
pubmed-meshheading:18458054-Receptors, Formyl Peptide,
pubmed-meshheading:18458054-Receptors, Lipoxin,
pubmed-meshheading:18458054-Tumor Necrosis Factor-alpha
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pubmed:year |
2008
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pubmed:articleTitle |
Identification of novel formyl peptide receptor-like 1 agonists that induce macrophage tumor necrosis factor alpha production.
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pubmed:affiliation |
Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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