REGULAR ARTICLEAdenosine Regulates Tissue Factor Expression on Endothelial Cells
Section snippets
Materials
Blood coagulation factor VIIa and factor X were kindly provided by Dr. Tomohiro Nakagaki of the Chemo-Sero-Theraputic Reserch Institute (Kumamoto, Japan). Thrombin was purchased from the Green Cross Corporation (Osaka, Japan). Recombinant human TNF was donated by the Asahi Chemical Industry (Shizuoka, Japan). The synthetic peptide substrate of factor Xa, N-benzoyl-L - isoleucyl - L - glutamyl - glycyl - L - arginine - p - nitro -anilide hydrochloride (S2222) was purchased from Chromogenix
Effect of Adenosine on the TF Activity on HUVECs Induced by TNF, Thrombin, or PMA
We previously reported that TNF, thrombin, and PMA induced TF expression on HUVECs in a dose- and time-dependent fashion [20]. In agreement with this, in the current study, TNF (1000 U/mL), thrombin (12.5 nM), or PMA (2.5 nM) induced TF expression on HUVEC surface, respectively (Figure 1A). Increasing concentrations of adenosine (0 to 10 μM) decreased TF activity in a dose-dependent fashion (Figure 1B). Incubation with 10 μM adenosine decreased the TF activity induced by TNF, thrombin, or PMA
Discussion
Adenosine is an active biological compound that modulates various physiological mechanisms such as cardiovascular tone and immune responses 1, 2, 3. During ischemic or chronic atherosclerotic processes, adenosine increases locally up to micromolar levels. It exerts anti-inflammatory and cytoprotective effects 1, 2, 3. In the current study, physiological concentrations of adenosine down-regulated the endothelial TF expression induced by TNF, thrombin, or PMA. This adenosine effect was
Acknowledgements
This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Culture and Sports of Japan (No. 09281215, 09480149, 09877206).
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