The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules

2.50
Hdl Handle:
http://hdl.handle.net/2336/2826
Title:
The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules
Authors:
Johnston, Andrew; Gudjonsson, Johann Eli; Sigmundsdottir, Hekla; Ludviksson, Bjorn Runar; Valdimarsson, Helgi
Citation:
Clin. Immunol. 2005, 114(2):154-63
Issue Date:
2005
Abstract:
Low-dose methotrexate (MTX) is an established and highly effective treatment for severe psoriasis and rheumatoid arthritis; however, its mechanism of action remains unclear. We investigated the effects of low-dose MTX on antigen-stimulated peripheral blood mononuclear cells and explored through which cellular pathways these effects are mediated. We show that MTX caused a dose-dependent suppression of T cell activation and adhesion molecule expression, and this was not due to lymphocyte apoptosis. The suppression of intercellular adhesion molecule (ICAM)-1 was adenosine and folate-dependent, while MTX suppression of the skin-homing cutaneous lymphocyte-associated antigen (CLA) was adenosine-independent. The effect of MTX on CLA, but not ICAM-1, required the constant presence of MTX in cultures. Thus, the suppression of T cell activation and T cell adhesion molecule expression, rather than apoptosis, mediated in part by adenosine or polyglutamated MTX or both, are important mechanisms in the anti-inflammatory action of MTX.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.sciencedirect.com/science/article/B6WCJ-4DTKKD8-2/1/4a2c4761eb92d552f8b48146bede0e3b

Full metadata record

DC FieldValue Language
dc.contributor.authorJohnston, Andrew-
dc.contributor.authorGudjonsson, Johann Eli-
dc.contributor.authorSigmundsdottir, Hekla-
dc.contributor.authorLudviksson, Bjorn Runar-
dc.contributor.authorValdimarsson, Helgi-
dc.date.accessioned2006-05-18T11:22:55Z-
dc.date.available2006-05-18T11:22:55Z-
dc.date.issued2005-
dc.identifier.citationClin. Immunol. 2005, 114(2):154-63en
dc.identifier.issn1521-6616-
dc.identifier.pmid15639649-
dc.identifier.doi10.1016/j.clim.2004.09.001-
dc.identifier.otherAAI12en
dc.identifier.urihttp://hdl.handle.net/2336/2826-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractLow-dose methotrexate (MTX) is an established and highly effective treatment for severe psoriasis and rheumatoid arthritis; however, its mechanism of action remains unclear. We investigated the effects of low-dose MTX on antigen-stimulated peripheral blood mononuclear cells and explored through which cellular pathways these effects are mediated. We show that MTX caused a dose-dependent suppression of T cell activation and adhesion molecule expression, and this was not due to lymphocyte apoptosis. The suppression of intercellular adhesion molecule (ICAM)-1 was adenosine and folate-dependent, while MTX suppression of the skin-homing cutaneous lymphocyte-associated antigen (CLA) was adenosine-independent. The effect of MTX on CLA, but not ICAM-1, required the constant presence of MTX in cultures. Thus, the suppression of T cell activation and T cell adhesion molecule expression, rather than apoptosis, mediated in part by adenosine or polyglutamated MTX or both, are important mechanisms in the anti-inflammatory action of MTX.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://www.sciencedirect.com/science/article/B6WCJ-4DTKKD8-2/1/4a2c4761eb92d552f8b48146bede0e3ben
dc.subjectAdenosineen
dc.subjectAnti-Inflammatory Agentsen
dc.subjectAntigens, Bacterialen
dc.subjectApoptosisen
dc.subjectCell Adhesion Moleculesen
dc.subjectFlow Cytometryen
dc.subjectFucosyltransferasesen
dc.subjectHumansen
dc.subjectIntegrinsen
dc.subjectIntercellular Adhesion Molecule-1en
dc.subjectLymphocyte Activationen
dc.subjectLymphocyte Activationen
dc.subjectMembrane Glycoproteinsen
dc.subjectMethotrexateen
dc.subjectRNA/geneticsen
dc.subjectRNA, Messengeren
dc.subjectReceptors, Interleukin-2en
dc.subjectReverse Transcriptase Polymerase Chain Reactionen
dc.subjectStreptococcus pyogenesen
dc.subjectT-Lymphocytesen
dc.titleThe anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion moleculesen
dc.typeArticleen
dc.format.digYES-

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