Xanthine oxidase does not mediate the antiproliferative effects of interferon-gamma in human umbilical vein endothelial cells.
Interferon-gamma (IFN-gamma) has potent antiproliferative effects on the endothelium, although the specific mechanisms responsible for this effect are not clear. We tested the hypothesis that suppression of endothelial cell proliferation by IFN-gamma is mediated by an increase in xanthine oxidase-derived O2-.. Human umbilical vein endothelial cells (HUVEC) were exposed to recombinant human IFN-gamma. We found that [3H]thymidine uptake decreased (p < 0.05) with increasing doses of IFN-gamma. Treatment of HUVEC with the xanthine oxidase inhibitor allopurinol or the O2-. scavenger superoxide dismutase had no effect (p > 0.05) on [3H]thymidine uptake of IFN-gamma-treated cells. In parallel, IFN-gamma decreased (p < 0.05) HUVEC cell counts, while allopurinol again had no effect (p > 0.05) on cell counts of IFN-gamma-treated or control HUVEC. In addition, xanthine oxidase activity of HUVEC did not (p > 0.05) increase following treatment with IFN-gamma. We conclude that IFN-gamma suppresses HUVEC proliferation by a mechanism independent of O2-. production by xanthine oxidase.
Terada
L S
LS
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262.
Arnold
P D
PD
D000493:Allopurinol / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides; D013936:Thymidine / Q000378:metabolism; D014471:Umbilical Veins; D014968:Xanthine Dehydrogenase / Q000187:drug effects; D014969:Xanthine Oxidase / Q000502:physiology*
D013481:Superoxides; D000493:Allopurinol; D007371:Interferon-gamma; D013482:Superoxide Dismutase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D013936:Thymidine