Copyright © 2006, European Society of Cardiology
Paracrine up-regulation of monocyte cyclooxygenase-2 by platelets: Role of transforming growth factor-β1
aE. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Italy
bCentro Cardiologico Monzino I.R.C.C.S, University of Milan, Italy
* Corresponding author. Department of Pharmacological Sciences, Via Balzaretti 9, 20133 Milan, Italy. Tel.: +39 02 50319913; fax: +39 02 50318250. Email address: susanna.colli{at}unimi.it
Objective: To examine the role of platelets and platelet-derived products on cyclooxygenase-2 (Cox-2) induction in adherent monocytes and to address the signaling pathways involved.
Methods: Platelets and monocytes were obtained from peripheral blood of healthy donors. Adherent monocytes were co-cultured with autologous platelets or platelet releasates or exposed to mediators contained in platelet 
-granules (either from platelet source or recombinant) for 4–24 h. Cox-2 protein and mRNA were determined by Western and RT-PCR analysis, respectively. Thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) synthesis as index of Cox-2 activity, and levels of transforming growth factor-β1 (TGF-β1) in platelet releasates were measured by enzyme immunoassay (EIA).
Results: Activated platelets induce rapid and transient Cox-2 de novo synthesis in adherent monocytes. The effect is dependent upon the platelet number but not upon cell–cell contact. Platelet-induced Cox-2 was not affected by prevention of platelet TxA2 synthesis or microparticle formation but was blunted by inhibition of platelet -granule secretion. TGF-β1, either platelet-derived or recombinant (rTGF-β1), induced Cox-2 expression and activity in adherent monocytes at concentrations within the range of those detected in releasates from activated platelets; this effect was not shared by recombinant platelet-derived growth factor (rPDGFBB). The time course of Cox-2 induction by TGF-β1 in monocytes was identical to that observed with platelet releasates. Moreover, TGF-β1 receptor blockade completely abolished platelet-induced Cox-2 expression. p38 MAPK activation represents a common transduction pathway through which activated platelets and rTGF-β1 induce Cox-2 in monocytes.
Conclusion: These findings suggest that TGF-β1 released by activated platelets has a pivotal role in Cox-2 induction in monocytes and further supports the key role of platelets in the inflammatory and reparative responses.
KEYWORDS Cyclooxygenase; Platelets; Growth factors; Monocytes; MAP-kinase
1 Current address: Unidad Mixta de Investigaciòn, University of Zaragoza, Spain.