Mycophenolate mofetil decreases endothelial prostaglandin E2 in response to allogeneic T cells or cytokines.
BACKGROUND
Prostaglandin E2 (PGE2) is a powerful endogenous immune suppressant and interferes with various T-cell functions. However, it is not known in detail whether immunosuppressive drugs influence the PGE2-driven immune response in transplant patients. Therefore, we investigated the effect of several immunosuppressive compounds, in particular the novel drug mycophenolate mofetil (MMF), on endothelial PGE2 release.


METHODS
Endothelial cells (HUVEC) were activated by either allogeneic CD4+ or CD8+ T cells, or by the cytokines interleukin-1 or gamma-interferon. Using an enzyme-linked immunosorbent assay, we analyzed PGE2 release of the activated HWEC in the presence of MMF, cyclosporine, or tacrolimus. As verapamil and mibefradil also possess immunosuppressive properties, they were included in the study as well.


RESULTS
Activation of HUVEC with interleukin-1 or T cells resulted in a drastic accumulation of PGE2 in the supernatant. Cyclosporine or tacrolimus had no effect on PGE2 release. However, Ca2+ channel blockers, when applied at higher dosages, caused a significant increase in PGE2. Interestingly, MMF strongly diminished the PGE2 level in the cell culture supernatant in a concentration-dependent manner.


CONCLUSIONS
The results demonstrate an inhibitory effect of MMF on PGE2 production, which may lower the benefits of the PGE2-triggered immune response after organ transplantation.
Blaheta
R A
RA
Department of General Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Nelson
K
K
Oppermann
E
E
Leckel
K
K
Harder
S
S
Cinatl
J
J
Weber
S
S
Shipkova
M
M
Encke
A
A
Markus
B H
BH
D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology
D016207:Cytokines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D015232:Dinoprostone; D016559:Tacrolimus