FTY720 inhibits S1P-mediated endothelial healing: relationship to S1P1-receptor surface expression

Biochemical and Biophysical Research Communications
Vera Krump-KonvalinkovaWolfgang Siess

Abstract

The phosphorylated derivative of the immunosuppressant FTY720 interacts with and modulates the function of sphingosine-1-phosphate (S1P)-receptors. We observed a significant reduction of endothelial surface binding of a S1P(1)-specific antibody after FTY720 treatment of 6h and longer, which was associated with a reduced healing after mechanic injury, impaired angiogenesis and enhanced adhesion molecule expression. FTY720 (5h) had no impact on the expression of S1P(1)- or S1P(3)-encoding transcripts. Notably, pre-treatment of cells with FTY720 for only 30min, which did not reduce S1P(1) surface expression, inhibited the rapid S1P- and SEW2871- (a S1P(1) agonist) induced cortical actin formation and cell migration. FTY720 was effective at concentrations as low as 5nM. FTY720 at therapeutic concentrations may be harmful by impairing important endothelial functions. Interestingly, FTY720 inhibited endothelial actin remodelling and cell migration without decreasing S1P(1) surface expression.

References

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Citations

Jan 19, 2010·American Journal of Respiratory Cell and Molecular Biology·Barry S SheaAndrew M Tager
Mar 2, 2013·American Journal of Respiratory Cell and Molecular Biology·Viswanathan NatarajanJoe G N Garcia
Dec 23, 2015·International Journal of Molecular Sciences·Michael K SchuhmannFelix Fluri
Feb 12, 2011·British Journal of Pharmacology·Mirjam SchuchardtMarkus van der Giet
Jun 28, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Dawei ZhangDong Huang
Jun 22, 2021·Tissue Barriers·Anke C Ziegler, Markus H Gräler

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