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

• Published in: Circulation research 1995-12, Vol.77 (6), p.1095-1106
• Main Authors: Wang, Weizheng, Chen, Hong Jun, Giedd, Kenneth N, Schwartz, Allan, Cannon, Paul J, Rabbani, LeRoy E
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Antigens - analysis; Aorta; Biological and medical sciences; Blood vessels and receptors; Cattle; Cell Movement - drug effects; Cells, Cultured; Culture Media; Fibrinolysis; Fundamental and applied biological sciences. Psychology; Humans; Interferon-gamma - pharmacology; Interleukin-4 - pharmacology; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Plasminogen Activators - pharmacology; Platelet-Derived Growth Factor - pharmacology; Protein C Inhibitor - analysis; Protein C Inhibitor - immunology; Thymidine - metabolism; Time Factors; Tissue Plasminogen Activator - biosynthesis; Tissue Plasminogen Activator - immunology; Tranexamic Acid - pharmacology; Up-Regulation; Urokinase-Type Plasminogen Activator - analysis; Urokinase-Type Plasminogen Activator - immunology; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.77.6.1095

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 (gamma-IFN) affect SMC fibrinolysis and migration, we examined the effects of human recombinant IL-4 and gamma-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 enzymelinked 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. 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 augmented PDGF induction of SMC TPA antigen. gamma-IFN inhibited PDGF induction of SMC TPA antigen and IL-4 potentiation of this process. gamma-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-IFN modulate the induction of SMC TPA and SMC migration by 2% fetal bovine serum and PDGF.(Circ Res. 1995;77:1095-1106.)