[Possible cytotoxic mechanisms of TNF in vitro].
TNF is a protein originally isolated by its ability to induce hemorrhagic necrosis of some tumors in vivo, and cytotoxic effects against certain tumor cells, but not against normal cells in vitro. Though mechanisms of the cytotoxicity and selectivity of TNF action in vitro are not clear, there is much evidence that free radicals such as superoxide and hydroxyl radicals, mediated by TNF, are correlated with TNF cytotoxicity. Recently, manganous superoxide dismutase (MnSOD) in mitochondria has been demonstrated to be a rescue protein against TNF cytotoxicity and to be induced when the cells are exposed to TNF in the resistant cells. Two steroid hormones, glucocorticoid and 1,25-dihydroxyvitamin D3, block the cytotoxicity of TNF. Glucocorticoid may reduce TNF cytotoxicity by inhibiting phospholipase A2 and 1,25-dihydroxyvitamin D3 by inducing MnSOD in combination with TNF.
Iwamoto
S
S
First Department of Biochemistry, School of Medicine, Showa University, Japan.
Takeda
K
K
D001095:Arachidonic Acids / Q000378:metabolism; D002762:Cholecalciferol / Q000494:pharmacology; D005609:Free Radicals; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use
D001095:Arachidonic Acids; D005609:Free Radicals; D005938:Glucocorticoids; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D002762:Cholecalciferol; D013482:Superoxide Dismutase