T-CELL LYMPHOKINES, INTERLEUKIN-4 AND GAMMA-INTERFERON, MODULATE THE INDUCTION OF VASCULAR SMOOTH-MUSCLE CELL TISSUE-PLASMINOGEN ACTIVATOR AND MIGRATION BY SERUM AND PLATELET-DERIVED GROWTH-FACTOR

Platelet-derived growth factor (PDGF)-induced smooth muscle cell (SMC) fibrinolysis is necessary for SMC migration. In order to determine wh ether the T-cell lymphokines interleukin-4, (IL-4) and gamma interfero n (gamma-IFN) affect SMC fibrinolysis and migration, we examined the e ffects of human recombinant IL-4 and gamma-IFN on human aortic SMC tis sue-type plasminogen activator (TPA), urokinase-type plasminogen activ ator (UPA), and plasminogen activator inhibitor a type-1 (PAI-1) antig en production, as determined by enzyme-linked immunosorbent assays. Al though IL-4 had no direct effect on SMC TPA antigen, IL-4 potentiated SMC TPA antigen levels and activity in conditioned media and cellular lysates in media containing 2% fetal bovine serum but did not change U PA or PAI-1 production. gamma-IFN attenuated IL-4 augmentation of SMC TPA antigen production in conditioned media, although gamma-IFN itself had no direct effects on SMC TPA and PAI-1 antigen production. IL-4 a ugmented PDGF induction of SMC TPA antigen. gamma-IFN inhibited PDGF i nduction of SMC TPA antigen and IL-4 potentiation of this process. gam ma-IFN diminished the promigratory effects of both IL-4 and PDGF on in vitro SMC migration. Tranexamic acid, a plasmin inhibitor, abrogated the stimulation of SMC migration by IL-4. Therefore, IL-4 and gamma-IF N modulate the induction of SMC TPA and SMC migration by 2% fetal bovi ne serum and PDGF.