THROMBIN-INDUCED DNA-SYNTHESIS OF CULTURED HUMAN DENTAL-PULP CELLS ISDEPENDENT ON ITS PROTEOLYTIC ACTIVITY AND MODULATED BY PROSTAGLANDIN E-2

To clarify the roles of alpha-thrombin and prostaglandin E-2 (PGE(2)) in the healing and inflammatory processes of dental pulp, their effect s on the DNA synthesis of human pulp cells were investigated by measur ement of [H-3]thymidine incorporation. At a concentration range of 1 t o 25 units/ml, alpha-thrombin stimulated DNA synthesis of the pulp cel ls by 1.5 to 2.6-fold. On the contrary, PGE, (>0.05 mu g/ml) suppresse d DNA synthesis by 24 to 39%. Using reverse transcriptase-polymerase c hain reaction, thrombin receptor mRNA expression was identified in the pulp cells. Furthermore, alpha-thrombin-induced DNA synthesis could b e inhibited by anti-thrombin III (2 units/ml) with heparin (2 units/ml ) or D-Phe-Pro-ArgCH(2)Cl (50 mu g/ml). PGE(2) (0.1 to 0.5 mu g/ml) al so inhibited the thrombin-induced DNA synthesis by 39 to 64%. These re sults imply that pulp cells express the thrombin receptor that is acti vated by the serine protease activity of thrombin. Interactions of thr ombin and PGE(2) are important in modulating the inflammatory and heal ing processes of the pulp.