The inhibition of DNA synthesis by prostaglandin E₂ in human gingival fibroblasts is independent of the cyclic AMP-protein kinase A signal transduction pathway

In this study we attempted to clarify the mechanism of the inhibitory effects of PGE₂ on DNA synthesis in Gin-1 (fibroblasts derived from healthy human gingiva) from the aspect of the cyclic AMP-dependent protein kinase signal transduction pathway. PGE₂ upregulated intracellular cyclic AMP accumulation and inhibited DNA synthesis in Gin-1 in a dose-dependent manner. When the PGE₂-induced intracellular cyclic AMP accumulation was further enhanced by treatment with the cyclic AMP-phosphodiesterase inhibitor, IBMX, the inhibitory effect of PGE₂ on DNA synthesis was also enhanced. Furthermore, when we examined the effects of forskolin, an activator of cyclic AMP production, on intracellular cyclic AMP accumulation and DNA synthesis, similar results were obtained. However, inhibitors of cyclic AMP-dependent protein kinase (protein kinase A) such as HA1004 did not diminish the inhibitory effect of PGE₂ on DNA synthesis in Gin-1. These results suggest that in Gin-1. PGE₂-induced cyclic AMP accumulation may not lead to the activation of protein kinase A or protein kinase A activity may not relate directly to the growth inhibitory effect of PGE₂, and that PGE₂ does not inhibit DNA synthesis through the cyclic AMP-protein kinase A signal transduction pathway in Gin-1.