Induction of cyclooxygenase-2 and enhanced release of prostaglandin E(2) and I(2) in human endothelial cells by engagement of CD40.
OBJECTIVE
The hypothesis was tested that CD40-CD154 interaction is involved in the induction of cyclooxygenase-2 and the release of prostanoids in human endothelial cells.


RESULTS
In a coculture model of human endothelial cells and a transfected CD154 positive cell line, engagement of CD40 on endothelial cells dramatically increased the synthesis of prostacyclin, prostaglandin E(2) and thromboxane A(2). This upregulation was mediated through an induction of cyclooxygenase-2 (Cox-2), as it was blocked by Cox-2-selective inhibitors. Western blot analysis demonstrated that Cox-2 protein was markedly increased in endothelial cells following CD40 engagement, an effect that was inhibited by pretreatment of cells with an anti-CD154 antibody.


CONCLUSIONS
The data indicate that signaling via CD40 constitutes a major pathway in human endothelial cells for the induction of Cox-2 and release of prostanoids. The CD40-Cox-2 axis thus may represent an important pathway for initiating or maintaining an inflammatory process at the vessel wall.
Garlichs
Christoph D
CD
Medical Clinic II, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany. christoph.garlichs@rzmail.uni-erlangen.de
Geis
Tobias
T
Goppelt-Struebe
Margarete
M
Eskafi
Saeed
S
Schmidt
Andrej
A
Schulze-Koops
Hendrik
H
Ludwig
Josef
J
Daniel
Werner G
WG
Schmeisser
Alexander
A
D015153:Blotting, Western; D019013:CD40 Antigens / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004790:Enzyme Induction; D011464:Epoprostenol / Q000032:analysis / Q000096:biosynthesis*; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D011336:Probability; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012680:Sensitivity and Specificity; D013928:Thromboxane A2 / Q000032:analysis / Q000096:biosynthesis*; D015854:Up-Regulation
D019013:CD40 Antigens; D007527:Isoenzymes; D008565:Membrane Proteins; D013928:Thromboxane A2; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone