936-17 Effects of Interleukin-4 and Gamma Interferon on Platelet-Derived Growth Factor Induction of Smooth Muscle Cell Fibrinolysis

Abstract

Interieukin-4 (IL-4) and gamma interferon (IFN- γ ) are cytokines made by two different activated T cell subsets which often manifest opposing biological effects. The induction of smooth muscle cell (SMC) production of tissue plasminogen activator (t-PA) by platelet-derived growth factor (PDGF) has been implicated in the pathologic process of vascular SMC migration in the arterial wall. We have previously demonstrated that, although IL-4 has no direct effect on SMC t-PA production, IL-4 increases the production of SMC t-PA antigen in culture media supplemented with 2% fetal bovine serum. IL-4 does not influence SMC production of plasminogen activator inhibitor-l (PAI-1). an endogenous inhibitor of t-PA, Moreover, IFN-y diminishes the augmentation of SMC t-PA antigen induced by IL-4. In order to determine whether the effects of PDGF on SMC t-PA and PAI-l production could be modulated by IL-4 and IFN- γ ), we examined the effects of IL-4 and IFN- γ ) on PDGF-treated human aortic SMC production of t-PA and PAI-l as determined by ELISAs for t-PA and PAI-l antigens in both SMC conditioned media and cellular Iysates: PDGF (ng/ml) IL-4 ( μ /ml) Conditioned Media Cellular Lysates t-PA (ng/10 5 cells) PAI-l (ng/l0 5 cells) t-PA (ng/10 5 cells) PAI-l (ng/10 5 cells) 0 0 0.164 145.0 0.550 25.0 10 0 0.321 217.8 0.601 27.7 10 500 0.498 † 204.1 0.773 †‡ 30.6 100 0 0.775 † 284.6 † 1.105 † 38.0 * 100 500 1.152 † ‡ 296.6 † 1.195 † 44.1 † n = 6 * P < 0.05 to control † p < 0.01 to control ‡ p < 0.01 to PDGF alone IL-4 potentiated PDGF induction of t-PA antigen. IL-4 and PDGF exerted only minimal effects on SMC PAI-l production. IFN- γ at doses of 10D-5000 u/ml blocked the augmentation of t-PA by IL-4 and PDGF. Taken together, these results suggest that IL-4 and IFN- γ may influence the fibrinolytic milieu of vascular SMC via interactions with PDGF.