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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1997-6-17
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pubmed:abstractText |
Interleukin-13 (IL-13) is a proinflammatory cytokine of T cell origin. Structural and functional studies suggest a key role for IL-13 in the genesis of chronic allergic inflammation; as such, its pharmacologic inhibition is of potential clinical utility. We studied the pharmacologic regulation of IL-13 expression by cyclic nucleotide phosphodiesterase (PDE) inhibitors in a panel of Amb a 1 (a major allergen of short ragweed, Ambrosia artemisiifolia)-specific T cell clones derived from a ragweed allergic, asthmatic subject. Proliferative responses of these cells were down-regulated by rolipram, a PDE4 inhibitor (% inhibitionMAX = 67%; IC50 = 20 microM). While the PDE3 inhibitor siguazodan provided no independent efficacy (IC50 > 10(-4) M), an increased efficacy of rolipram in the presence of 10(-5) M siguazodan was noted at 10(-6), 10(-5), and 10(-4) M rolipram (P < 0.03, 0.01, and 0.04, respectively). The EC50 values remained unchanged between assays using the PDE4 inhibitor with or without the PDE3 inhibitor. Both IL-13 gene expression and protein secretion into culture supernatants were down-regulated by the PDE4 inhibitor (P < or = 0.005). Once again, the use of a PDE3 inhibitor provided no independent efficacy (P > or = 0.2), and in this instance, increased efficacy of the PDE4 inhibitor with the PDE3 inhibitor was not apparent (P > or = 0.3). IL-13 production from clones with Th0, Th1, and Th2 phenotypes appeared equally sensitive to treatment with the PDE4 inhibitor. We conclude that the anti-inflammatory effects of PDE4 inhibitors may be mediated, in part, by down-regulation of IL-13.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3',5'-Cyclic-AMP Phosphodiesterases,
http://linkedlifedata.com/resource/pubmed/chemical/Allergens,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanidines,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-13,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridazines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidinones,
http://linkedlifedata.com/resource/pubmed/chemical/Rolipram,
http://linkedlifedata.com/resource/pubmed/chemical/siguazodan
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1055-60
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9174120-3',5'-Cyclic-AMP Phosphodiesterases,
pubmed-meshheading:9174120-Allergens,
pubmed-meshheading:9174120-Clone Cells,
pubmed-meshheading:9174120-Gene Expression,
pubmed-meshheading:9174120-Glycoproteins,
pubmed-meshheading:9174120-Guanidines,
pubmed-meshheading:9174120-Humans,
pubmed-meshheading:9174120-Interleukin-13,
pubmed-meshheading:9174120-Lymphocyte Activation,
pubmed-meshheading:9174120-Lymphocytes,
pubmed-meshheading:9174120-Phosphodiesterase Inhibitors,
pubmed-meshheading:9174120-Pyridazines,
pubmed-meshheading:9174120-Pyrrolidinones,
pubmed-meshheading:9174120-Rolipram
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pubmed:year |
1997
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pubmed:articleTitle |
Regulation of interleukin-13 by type 4 cyclic nucleotide phosphodiesterase (PDE) inhibitors in allergen-specific human T lymphocyte clones.
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pubmed:affiliation |
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, U.S.A.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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