Abstract
We investigated the effect of recombinant tumor necrosis factor-alpha (rTNF-α) on the proliferative response of human umbilical vein endothelial cells (HUVEC) to normal human serum (NHS), in the absence or the presence of interferon (IFN)-γ. rTNF-α significantly impaired NHS-stimulated HUVEC growth at a dose as low as 0.1 U/ml. The inhibitory effect of rTNF-α was dose-dependent up to 50-100 U/ml and was already evident after 2 h of incubation. Doses of rTNF-α in the range of 10 U/ml completely suppressed 3H-thymidine uptake stimulated by 7.5% NHS, and the effect was partially overcome by 10-20% NHS. rTNF-α was not cytotoxic at doses up to 1000 U/ml. rIFN-γ was also effective in suppressing NHS-stimulated3H-thymidine incorporation, and at low doses (0.1 U/ml) rIFN-γ and rTFN-α showed an additive effect. The effect of TFN-α and IFN-γ in antagonizing the proliferative response of vascular endothelium to the variety of growth factors contained in human serum could be relevant in a variety of pathologic conditions involving endothelium damage and proliferation.
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