[Effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain]

We studied the effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain. Microvascular endothelial cells were derived from the endothelial cells of gerbil brain. First, effects of tumor necrosis factor (TNF) or [3H] thymidine up-take by the endothelial cells and human smooth muscle cells were studied. After 4 days exposure to TNF, 50 microCi/ml of [3H] thymidine were added to these cells. [3H] thymidine up-take by the endothelial cells were suppressed by adding TNF dose-dependently. Especially, [3H] thymidine up-take by endothelial cells cultured with 1000 U/ml TNF for 4 days were 25 to 62% of the control values. These cells exposed to 1000 U/ml TNF, furthermore, became spindlelike in appearance and over up each other. But, TNF had no effect on human smooth muscle cells. Second, instead of TNF, interferon-gamma (gamma IFN) were studied in the same way. But, [3H] thymidine up-take by the endothelial cells were not effected by adding gamma IFN. Third, the supernatant of the cultured glioma cells were studied in the same way. The supernatants of 6 glioma cells in 8 cases showed TNF like activity to the endothelial cells of gerbil brain. These supernatants, that is, suppressed [3H] thymidine up-take by the endothelial cells over 50%. These suppression were, furthermore, released by adding 50 microliter anti-TNF antibodies. So, we found the cytotoxic effects of TNF on the endothelial cells of gerbil brain. The supernatants of glioma cells, also, showed TNF like activity to the endothelial cells.