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(Circulation Research. 1995;77:1095-1106.)
© 1995 American Heart Association, Inc.

Articles

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

Weizheng Wang, Hong Jun Chen, Kenneth N. Giedd, Allan Schwartz, Paul J. Cannon, LeRoy E. Rabbani

From the Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY.

Correspondence to LeRoy E. Rabbani, MD, Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th St, New York, NY 10032.

Abstract Platelet-derived growth factor (PDGF)–induced smooth muscle cell (SMC) fibrinolysis is necessary for SMC migration. In order to determine whether the T-cell lymphokines interleukin-4 (IL-4) and gamma interferon (-IFN) affect SMC fibrinolysis and migration, we examined the effects of human recombinant IL-4 and -IFN on human aortic SMC tissue-type plasminogen activator (TPA), urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) antigen production, as determined by enzyme-linked immunosorbent assays. Although 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 UPA or PAI-1 production. -IFN attenuated IL-4 augmentation of SMC TPA antigen production in conditioned media, although -IFN itself had no direct effects on SMC TPA and PAI-1 antigen production. IL-4 augmented PDGF induction of SMC TPA antigen. -IFN inhibited PDGF induction of SMC TPA antigen and IL-4 potentiation of this process. -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 -IFN modulate the induction of SMC TPA and SMC migration by 2% fetal bovine serum and PDGF.

Key Words: • interleukin-4 • fibrinolysis • gamma interferon • platelet-derived growth factor • smooth muscle cells

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