Induction and release of manganese superoxide dismutase from mitochondria of human umbilical vein endothelial cells by tumor necrosis factor-alpha and interleukin-1 alpha.

The effects of tumor necrosis factor-alpha (TNF alpha) on cultured human umbilical vein endothelial cells (EC) and 2 cancer cell lines, A549 and ME180, were compared. The effects of interleukin-1 alpha (IL-1 alpha) on EC were also examined. While A549 cells were fairly resistant to the cytolytic effects of TNF alpha and IL-1 alpha, ME180 cells were sensitive. EC were also less sensitive to TNF alpha than ME180 cells, as judged by viability of individual cells and by the release of lactate dehydrogenase (LDH) into the medium. Both manganese superoxide dismutase (Mn-SOD) and its mRNA were markedly induced by these cytokines in EC and in A549 cells but not in ME180 cells. The levels of Mn-SOD in the conditioned medium of EC were markedly increased after stimulation with cytokines, whereas those in ME180 and A549 cells were relatively low. The amount of Mn-SOD released appears to be comparable to that from cells lysed due to the cytocidal effect of cytokines, as assessed by measuring intra- and extra-cellular LDH activity. These data suggest that, in vivo, the TNF alpha and IL-1 alpha produced by cancer cells and other cells may induce Mn-SOD in vascular endothelial cells as well as other host tissues, resulting in release of a relatively large amount of this protein into the serum.