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rdf:type |
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lifeskim:mentions |
umls-concept:C0004096,
umls-concept:C0014457,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0079189,
umls-concept:C0205087,
umls-concept:C0205390,
umls-concept:C0439799,
umls-concept:C0458827,
umls-concept:C0599779,
umls-concept:C0871261,
umls-concept:C1292733,
umls-concept:C1456443,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1999216,
umls-concept:C2911692
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pubmed:issue |
2-3
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pubmed:dateCreated |
2007-3-9
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pubmed:abstractText |
T cells play a regulatory role in the pathogenesis of various immune and allergic diseases, including human asthma. Recently, it was reported that a pyrazole derivative, YM-58483 (BTP2), potently inhibits Ca(2+) release-activated Ca(2+) (CRAC) channels and interleukin (IL)-2 production in T cells. We investigated the effects of YM-58483 on T helper type 2 (Th2) cytokine production in vitro and antigen-induced airway asthmatic responses in vivo. YM-58483 inhibited IL-4 and IL-5 production in a conalbumine-stimulated murine Th2 T cell clone (D10.G4.1), and IL-5 production in phytohemagglutinin-stimulated human whole blood cells with IC(50) values comparable to those reported for its CRAC channel inhibition (around 100 nM). YM-58483 inhibited antigen-induced eosinophil infiltration into airways, and decreased IL-4 and cysteinyl-leukotrienes content in inflammatory airways induced in actively sensitized Brown Norway rats. Furthermore, orally administered YM-58483 prevented antigen-induced late phase asthmatic bronchoconstriction and eosinophil infiltration in actively sensitized guinea pigs. These data suggest that the inhibition of Ca(2+) influx through CRAC channel leads to the prevention of antigen-induced airway inflammation, probably via the inhibition of Th2 cytokine production and inflammatory mediators release. YM-58483 may therefore be useful for treating airway inflammation in bronchial asthma.
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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 |
Apr
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pubmed:issn |
0014-2999
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
560
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
225-33
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pubmed:meshHeading |
pubmed-meshheading:17307161-Anilides,
pubmed-meshheading:17307161-Animals,
pubmed-meshheading:17307161-Antigens,
pubmed-meshheading:17307161-Asthma,
pubmed-meshheading:17307161-Calcium,
pubmed-meshheading:17307161-Calcium Channels,
pubmed-meshheading:17307161-Disease Models, Animal,
pubmed-meshheading:17307161-Dose-Response Relationship, Drug,
pubmed-meshheading:17307161-Eosinophilia,
pubmed-meshheading:17307161-Female,
pubmed-meshheading:17307161-Guinea Pigs,
pubmed-meshheading:17307161-Humans,
pubmed-meshheading:17307161-Interleukin-4,
pubmed-meshheading:17307161-Interleukin-5,
pubmed-meshheading:17307161-Male,
pubmed-meshheading:17307161-Mice,
pubmed-meshheading:17307161-Mice, Inbred C3H,
pubmed-meshheading:17307161-Mice, Inbred C57BL,
pubmed-meshheading:17307161-Rats,
pubmed-meshheading:17307161-Rats, Inbred BN,
pubmed-meshheading:17307161-Thiadiazoles
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pubmed:year |
2007
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pubmed:articleTitle |
YM-58483, a selective CRAC channel inhibitor, prevents antigen-induced airway eosinophilia and late phase asthmatic responses via Th2 cytokine inhibition in animal models.
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pubmed:affiliation |
Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. taiji.yoshino@jp.astellas.com
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pubmed:publicationType |
Journal Article
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