SERINE-PROTEASE ACTIVITY IS ESSENTIAL FOR THROMBIN-INDUCED PROTEIN-SYNTHESIS IN CULTURED HUMAN DENTAL-PULP CELLS - MODULATION ROLES OF PROSTAGLANDIN E-2

Irritations and injuries to the dental pulp usually lead to different degrees of pulpal inflammation. To investigate the roles of thrombin a nd prostaglandins in the healing and inflammatory processes of dental pulp as well as their effects on pulpal protein synthesis, human denta l pulp cell cultures were established and their protein production was measured with or without the presence of exogenous thrombin and prost aglandins. At concentrations of 1-25 U/ml, alpha-thrombin increased th e protein synthesis to 1.4-2.3 fold over the vehicle control. On the c ontrary, 0.1 mu g/ml of prostaglandin E-1 (PGE(1)) suppressed protein synthesis by 60%. Prostaglandin E-2 (PGE2) also inhibited protein synt hesis with an IC50 of 0.4 mu g/ml. The stimulatory effects of thrombin (10 U/ml) can be inhibited by antithrombin III (2 U/ml) (a natural th rombin inhibitor) with heparin (2 U/ml), PPACK (D-Phe-Pro-ArgCH(2)Cl) (20-50 mu g/ml) (a serine protease inhibitor), and PGE(2) (0.5-1.0 mu g/ml). Moreover, TRAP (20-40 mu g/ml), a thrombin receptor agonist pep tide, also exerted a stimulatory effect (1.21-1.37 fold). In conclusio n, thrombin-induced protein synthesis by pulp cells is dependent on pr oteolytic activity, but not on binding to receptors. Both PGE(1) and P GE(2) exert suppressive effects on protein synthesis, indicating that interactions between thrombin and prostaglandins are important in regu lating the inflammation, repair and regeneration of pulp tissue follow ing injury.