Prostaglandins and fibroblast functions in vitro

Abstract

Secondary embryonic mouse fibroblasts synthesise mainly E-type PG. The formation of PGF2 alpha is about 10 times lower. No PGI2 formation was observed. Secondary embryonic mouse fibroblasts possess an adenylate cyclase which is stimulated by E-type PGs, but little by PGF2 alpha or PGI2. PGE1-induced stimulation of cAMP levels is dose-dependently linked to an increase in biosynthetic activity of the cells, visible in increased GAG biosynthesis and PG formation. cAMP-dependent enhancement of GAG biosynthesis does not alter the carbohydrate spectrum of the secreted GAG, indicating that only the amount, but not the quality of the secreted GAG is affected by PGE1 or cAMP. Steroidal as well as non-steroidal antirheumatic agents can affect either basal or PGE1 stimulated cAMP levels or other components of the adenylate cyclase system independent of their inhibitory action on PG formation. These effects are always reflected in a decrease or increase of GAG biosynthesis. PGE1-induced stimulation of cAMP levels is related to an inhibition of fibroblast proliferation. Reduction of endogenous PG formation for prolonged periods does not result in a prolonged decrease of intracellular cAMP followed by a decrease in GAG biosynthesis or an increase in proliferation. The initial effect of reduced endogenous PG formation is compensated for by an increased sensitivity of the cells to PG's, resulting in maintenance of basal cAMP levels and an increased sensitivity to exogenous PGE1. These effects on cAMP levels are also reflected in GAG biosynthesis and proliferative activity of the cells.