The drug pump multi-drug resistance protein 1 (MRP1) is induced upon T cell activation and its inhibition blocks T cell function - 25/08/11
Abstract |
Rationale |
We observed that activated T cells have increased activity of MRP1 by virtue of rapid extrusion of its fluorescent substrates. We asked whether MRP1 is expressed during T cell activation and whether it might be a target for modulation of the T cell response.
Methods |
We tested for expression and function of MRP1 on adult human PBMC using RT-PCR and fluorescent dye extrusion studies, respectively. PBMC were stimulated with the superantigen TSST-1 (10 ng/ml) and the chemokine SDF-1 in the absence and presence of the MRP1 inhibitor MK-571, and tested for inhibition of T cell function.
Results |
MRP1 is selectively expressed on memory T cells, compared with naïve and cord blood T cells, and is up-regulated during activation. MK-571 blocks TSST-1-induced morphologic changes and the expression of the activation marker CD69, and of IFN-γ, TNF-⍺, IL-10, and IL-2, in a dose dependent manner. Activation blockade was reversible upon withdrawal of MK-571. MRP1 inhibition also blocked calcium flux in CD4 T cells in response to T cell receptor stimulation with anti-CD3, and calcium flux and chemotaxis in response to stimulation with the chemokine SDF-1.
Conclusions |
MRP1 may be a target for reversible inhibition of T cell activation, and may provide insight into signaling pathways necessary for T cell function.
Le texte complet de cet article est disponible en PDF. | Funding: FDA |
Vol 113 - N° 2S
P. S249 - février 2004 Retour au numéro
Article précédent
- Time course of allergen induced nitric oxide synthase mRNA expression in mice model of anaphylaxis
- K. Sade, S. Etkin, S. Kivity
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- J.A. Eckman, S. Konno, S. Huang
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