Serine protease activity is essential for thrombin‐induced protein synthesis in cultured human dental pulp cells: modulation roles of prostaglandin E₂

Abstract

Chang MC, Lan WH, Chan CP, Lin CP, Hsieh CC, Jeng JH: Serine protease activity is essential for thrombin‐induced protein synthesis in cultured human dental pulp cells: modulation roles of prostaglandin E2. J Oral Pathol Med 1998; 27: 23–9. © Munksgaard, 1998. Irritations and injuries to the dental pulp usually lead to different degrees of pulpal inflammation. To investigate the roles of thrombin and prostaglandins in the healing and inflammatory processes of dental pulp as well as their effects on pulpal protein synthesis, human dental pulp cell cultures were established and their protein production was measured with or without the presence of exogenous thrombin and prostaglandins. At concentrations of 1–25 U/ml, a‐thrombin increased the protein synthesis to 1.4–2.3 fold over the vehicle control. On the contrary, 0.1 (μg/ml of prostaglandin E] (PGE1 suppressed protein synthesis by 60%. Prostaglandin E2 (PGE2) also inhibited protein synthesis with an IC50 of 0.4 ug/ml. The stimulatory effects of thrombin (10 U/ml) can be inhibited by antithrombin III (2 U/ml) (a natural thrombin inhibitor) with heparin (2 U/ml), PPACK (D‐Phe‐Pro‐ArgCH2Cl) (20–50 ug/ml) (a serine protease inhibitor), and PGE2 (0.5–1.0 μg/ml). Moreover, TRAP (20–40 μg/ml), a thrombin receptor agonist peptide, also exerted a stimulatory effect (1.21–1.37 fold). In conclusion, thrombin‐induced protein synthesis by pulp cells is dependent on proteolytic activity, but not on binding to receptors. Both PGE1 and PGE2 exert suppressive effects on protein synthesis, indicating that interactions between thrombin and prostaglandins are important in regulating the inflammation, repair and regeneration of pulp tissue following injury.

Cytokine‐induced prostaglandin E2 production and cyclooxygenase‐2 expression in dental pulp cells: downstream calcium signalling via activation of prostaglandin EP receptor

“…This can be due to the induction of COX‐2 gene expression and subsequent PGE 2 production by these cytokines. The activation of COX and PGE 2 production has been shown to suppress DNA and protein synthesis of pulp cells (Chang et al. 1998a,b).…”

“…1998a,b). In addition, PGE 2 inhibits the IL‐1 β and TNF‐ α ‐induced MMP‐1 mRNA expression (Chang et al. 1998b, Lin et al.…”

“…The activation of COX and PGE 2 production has been shown to suppress DNA and protein synthesis of pulp cells (Chang et al 1998a,b). In addition, PGE 2 inhibits the IL-1b and TNF-a-induced MMP-1 mRNA expression (Chang et al 1998b, Lin et al 2001. PGE 2 is also shown to stimulate glycosaminoglycan (GAG) synthesis and alkaline phosphatase activity of pulp cells , Hamasaki et al 1992.…”

“…Two strains of human dental pulp cells were established. Cultured dental pulp cells are spindle shape with extended cellular processes but show marked alkaline phosphatase activities, indicating their potential for tissue mineralization (Chang et al. 1998a,b, Chan et al.…”

“…1998a). The stimulatory effects of thrombin (10 U mL −1 ), a vascular coagulation factor, can be inhibited by PGE 2 (Chang et al. 1998a,b).…”