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Background/purposes: TGF-β1 is an important growth factor that may influence the odontoblast differentiation and matrix deposition in the reactionary/reparative dentinogenesis to dental caries or other tooth injuries. TGF-β1 exerts its effects through various signaling pathways, such as Smads and MAPKs. Cyclooxygenase-2 (COX-2) is a membrane-associated enzyme that produces prostaglandin E2 (PGE2) at sites of pulpal injury and inflammation, which leads to tissue swelling, redness and pain. The purposes of this study were to investigate the differential signal transduction pathways of TGF-β1 that mediate COX-2 stimulation and PGE2 production in dental pulp cells.Methods: Pulp cells were exposed to TGF-β1 with/without SB431542 (an ALK5/Smad2 inhibitor) and U0126 (a MEK/ERK inhibitor). MTT assay was used to estimate cell viability. Enzyme-linked immunosorbent assay (ELISA) was used for measurement of PGE2 levels. RT-PCR and western blot were used to determined COX-2 mRNA and protein, respectively.Results: Exposure to TGF-β1 (1-10 ng/ml) increased the COX-2 mRNA and protein level of cultured pulp cells. Exposure to TGF-β1 (0.1-10 ng/mL) significantly stimulated PGE2 production of dental pulp cells. Under the pretreatment of SB431542, the stimulatory effect of TGF-β1 on COX-2 level of pulp cells was inhibited. Similarly, U0126 also partly inhibited the TGF-β1-induced COX-2 expression.Conclusion: TGF-β1 increased the COX-2 and PGE2 level of cultured pulp cells. The effect of TGF-β1 on COX-2 protein expression was associated with ALK5/Smad2/3 and MEK/ERK pathways. These events are important in the early inflammation, repair and regeneration of dental pulp in response to injury. [ABSTRACT FROM AUTHOR]

Catechol (benzenediol) is present in plant-derived products, such as vegetables, fruits, coffee, tea, wine, areca nut and cigarette smoke. Because platelet dysfunction is a risk factor of cardiovascular diseases, including stroke, atherosclerosis and myocardial infarction, the purpose of this study was to evaluate the anti-platelet and anti-inflammatory effect of catechol and its mechanisms. The effects of catechol on cyclooxygenase (COX) activity, arachidonic acid (AA)-induced aggregation, thromboxane B2 (TXB2) production, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production and extracellular signal-regulated kinase (ERK)/p38 phosphorylation were determined in rabbit platelets. In addition, its effect on IL-1β-induced prostaglandin E2 (PGE2) production by fibroblasts was determined. The ex vivo effect of catechol on platelet aggregation was also measured. Catechol (5-25 µM) suppressed AA-induced platelet aggregation and inhibited TXB2 production at concentrations of 0.5–5 µM; however, it showed little cytotoxicity and did not alter U46619-induced platelet aggregation. Catechol (10–50 µM) suppressed COX-1 activity by 29–44% and COX-2 activity by 29–50%. It also inhibited IL-1β-induced PGE2 production, but not COX-2 expression of fibroblasts. Moreover, catechol (1–10 µM) attenuated AA-induced ROS production in platelets and phorbol myristate acetate (PMA)-induced ROS production in human polymorphonuclear leukocytes. Exposure of platelets to catechol decreased AA-induced ERK and p38 phosphorylation. Finally, intravenous administration of catechol (2.5–5 µmole/mouse) attenuated ex vivo AA-induced platelet aggregation. These results suggest that catechol exhibited anti-platelet and anti-inflammatory effects, which were mediated by inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation. The anti-platelet effect of catechol was confirmed by ex vivo analysis. Exposure to catechol may affect platelet function and thus cardiovascular health. [ABSTRACT FROM AUTHOR]