Effects of interferons \u3b1/\u3b2 on the proliferation of human micro- and macrovascular endothelial cells

Synthetic interferons (IFNs) are used in the treatment of several types of cancer. In addition to an antitumor effect, IFNs show antiangiogenic activity. The aim of this study was to investigate the effects of IFN-\u3b1 and IFN-\u3b2 on human micro- and macrovascular endothelial cells in vitro [human micro vascular lung endothelial cells (HMVEC-L) and human umbilical cord endothelial cells (HUVEC)]. By immunohistochemical staining and quantitative reverse transcriptase (RT)-polymerase chain reaction, we studied expression of type I IFN receptors. We evaluated the effects of IFN-\u3b1 and IFN-\u3b2 on the proliferation (DNA content), apoptosis (DNA fragmentation by enzyme-linked immunosorbent assay), and cell cycle distribution (flow-cytometric analysis) of endothelial cells. HUVEC and HMVEC-L cells show comparable expression level of the distinct IFN receptor subtypes. Proliferation of HMVEC-L and HUVEC was inhibited by IFN-\u3b2 (the half maximal inhibitory concentration [IC(50)]\u2009=\u200960 and 90\u2009IU/mL, respectively), but not by IFN-\u3b1 at a dose up to 1,000\u2009IU/mL. An interesting and unexpected observation was an inhibition of apoptosis by IFN-\u3b2. After 72\u2009h of treatment with IFN-\u3b2. Cell cycle inhibition occurs in late S-phase in both cell lines. In conclusion, only IFN-\u3b2, not IFN-\u3b1 (10-1,000\u2009IU/mL), has an inhibitory activity on endothelial cell proliferation. Surprisingly, apoptosis was decreased by IFN treatment, whereas inhibition of proliferation is caused by cell cycle arrest in late S-phas