Synovial Cell Activation. Studies on the Mechanism of Action of Synovial Activator Activity

Synovial activator (SA) from peripheral blood mononuclear cells stimulates the plasminogen activator (PA) levels of human synovial fibroblasts. Using the sensitive technique of transcriptional inhibition followed by a prolonged translation period, data suggested that the first synthesis of mRNA needed for the increase in PA activity began within 40-60 min; this increase in protease activity was reversible on removal of SA from the cultures and also declined after about 3 days even if SA was not withdrawn. The RNA dependent events necessary for the synovial cell activation were to a large extent completed by about 4-8 h while those dependent on protein synthesis lasted for about 12 h. The effectiveness of suboptimal concentrations of SA could be potentiated by all-trans retinoic acid. A similar potentiation was effected by phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine and theophylline, by 8-bromo-cAMP, and by prostaglandins of the E and F series; these last observations suggest cyclic nucleotide involvement in the SA-mediated elevation of synovial fibroblast PA activity.