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

Andrew Johnston; Johann Eli Gudjonsson; Hekla Sigmundsdottir; Björn Runar Ludviksson; Helgi Valdimarsson

doi:10.1016/j.clim.2004.09.001

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

Andrew Johnston, Johann Eli Gudjonsson, Hekla Sigmundsdottir, Björn Runar Ludviksson, Helgi Valdimarsson

Research output: Contribution to journal › Article › peer-review

189 Citations (Scopus)

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.

Original language	English
Pages (from-to)	154-163
Number of pages	10
Journal	Clinical Immunology
Volume	114
Issue number	2
DOIs	https://doi.org/10.1016/j.clim.2004.09.001
Publication status	Published - Feb 2005

Bibliographical note

Funding Information:
This work was supported by the Icelandic Research Council and the Icelandic Graduate Training Fund. We would like to thank Arna A. Antonsdóttir, Ari Kárason and Ásta Solilja Gudmundsdóttir at deCODE Genetics for help with the TaqMan RT-PCR.

Other keywords

Adenosine
Apoptosis
CLA
ICAM-1
Methotrexate
Psoriasis

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

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.",

keywords = "Adenosine, Apoptosis, CLA, ICAM-1, Methotrexate, Psoriasis",

author = "Andrew Johnston and Gudjonsson, {Johann Eli} and Hekla Sigmundsdottir and {Runar Ludviksson}, Bj{\"o}rn and Helgi Valdimarsson",

note = "Funding Information: This work was supported by the Icelandic Research Council and the Icelandic Graduate Training Fund. We would like to thank Arna A. Antonsd{\'o}ttir, Ari K{\'a}rason and {\'A}sta Solilja Gudmundsd{\'o}ttir at deCODE Genetics for help with the TaqMan RT-PCR.",

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AU - Sigmundsdottir, Hekla

AU - Runar Ludviksson, Björn

AU - Valdimarsson, Helgi

N1 - Funding Information: This work was supported by the Icelandic Research Council and the Icelandic Graduate Training Fund. We would like to thank Arna A. Antonsdóttir, Ari Kárason and Ásta Solilja Gudmundsdóttir at deCODE Genetics for help with the TaqMan RT-PCR.

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AB - 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.

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

Abstract

Bibliographical note

Other keywords

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