Paracrine up-regulation of monocyte cyclooxygenase-2 by platelets: role of transforming growth factor-beta1

• Published in: Cardiovascular research Vol. 74; no. 2; pp. 270 - 278
• Main Authors: Eligini, Sonia, Barbieri, Silvia S, Arenaz, Izaskun, Tremoli, Elena, Colli, Susanna
• Format: Journal Article
• Language: English
• Published: England 01.05.2007
• Subjects: Biomarkers - analysis; Blood Platelets - metabolism; Blotting, Western - methods; Cell Adhesion; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase 2 - metabolism; Dinoprostone - analysis; Humans; Monocytes - enzymology; Paracrine Communication - physiology; Platelet Activation; Reverse Transcriptase Polymerase Chain Reaction; Thromboxane B2 - analysis; Transforming Growth Factor beta1 - analysis; Transforming Growth Factor beta1 - metabolism; Up-Regulation; Wound Healing - physiology
• ISSN: 0008-6363

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. 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 alpha-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-beta1 (TGF-beta1) in platelet releasates were measured by enzyme immunoassay (EIA). 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 alpha-granule secretion. TGF-beta1, either platelet-derived or recombinant (rTGF-beta1), 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-beta1 in monocytes was identical to that observed with platelet releasates. Moreover, TGF-beta1 receptor blockade completely abolished platelet-induced Cox-2 expression. p38 MAPK activation represents a common transduction pathway through which activated platelets and rTGF-beta1 induce Cox-2 in monocytes. These findings suggest that TGF-beta1 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.