Modulation of synovial fibroblast plasminogen activator and plasminogen activator inhibitor production by protein kinase C.

Biochim Biophys Acta 1991 Nov 21;1097(4):283-8  

Uhl J; Newton RC; Gross JL; Rommi W; Mochan E
Department of Inflammation, Sterling Research Group, Rennselaer, NY 12144.

Phorbol myristate acetate (PMA) added to human synovial fibroblast cultures caused a dose- dependent increase in the production of plasminogen activator inhibitor- type 1 (PAI- 1 ). In addition, PMA inhibited endogenous and interleukin- 1 (IL- 1 ) induced plasminogen activator (PA) activity, while increasing mRNA PAI- 1 levels. Other protein kinase C (PKC) activators , mezerein and teleocidin B4, caused similar effects. The simultaneous addition of the PKC antagonists, H-7 or staurosporine, prevented the inhibition of PA activity by PMA. This study shows that activation of PKC inhibits PA and stimulates PAI production in human synovial fibroblasts . These results suggest that activation of PKC may play an important role in regulating increased PA production associated with joint destruction in rheumatoid arthritis (RA).