Linked Life Data

15922994

Source:http://linkedlifedata.com/resource/pubmed/id/15922994

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-7-4
pubmed:abstractText
Tropisetron, an antagonist of serotonin type 3 receptor, has been investigated in chronic inflammatory joint process. Since T cells play a key role in the onset of several inflammatory diseases, we have evaluated the immunosuppressive activity of tropisetron in human T cells, discovering that this compound is a potent inhibitor of early and late events in TCR-mediated T cell activation. Moreover, we found that tropisetron specifically inhibited both IL-2 gene transcription and IL-2 synthesis in stimulated T cells. To further characterize the inhibitory mechanisms of tropisetron at the transcriptional level, we examined the DNA binding and transcriptional activities of NF-(kappa)B, NFAT and AP-1 transcription factors in Jurkat T cells. We found that tropisetron inhibited both the binding to DNA and the transcriptional activity of NFAT and AP-1. We also observed that tropisetron is a potent inhibitor of PMA plus ionomycin-induced NF-(kappa)B activation but in contrast TNF(alpha)-mediated NF-(kappa)B activation was not affected by this antagonist. Finally, overexpression of a constitutively active form of calcineurin indicated that this phosphatase may represent one of the main targets for the inhibitory activity of tropisetron. These findings provide new mechanistic insights into the anti-inflammatory activities of tropisetron, which are probably independent of serotonin receptor signalling and highlight their potential to design novel therapeutic strategies to manage inflammatory diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
369-80
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
The 5-HT3 receptor antagonist tropisetron inhibits T cell activation by targeting the calcineurin pathway.
pubmed:affiliation
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Avda Menendez Pidal, s/n, 14004 Córdoba, Spain.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't