Expression of the p75 TNF receptor is linked to TNF-induced NFkappaB translocation and oxyradical neutralization in glial cells.

摘要: Tumor necrosis factor (TNF)-family cytokines induce reactive oxygen species (ROS) that injure vulnerable populations of brain cells. Among glia, oligodendrocytes are particularly susceptible to TNF-induced ROS whereas microglia protected. We previously found in vitro predominantly express the p55 type-1 TNF receptor, while microglial cells both and p75 type-2 receptors. hypothesized differential receptor expression attendant signaling underlies relative vulnerability oligodendrocytes, versus microglia, injury. To test this hypothesis, purified cultures glial were incubated 0-48 hr with TNFalpha or lymphotoxin-alpha, following which levels ROS, glutathione (GSH), nuclear kappa-B (NFkappaB) translocation, anti-oxidant proteins activity measured. 48 exposure increased 28% decreased GSH 17% but 24% 112% increase microglia. Thirty 180 min NFkappaB translocation a greater extent for longer time was followed 24-48 later 3- 13-fold increases manganese superoxide dismutase protein 6-fold enzyme activity. Collectively, these data suggest signals transduced through activate mechanisms protect from Lacking such signals, considerably more injurious effects TNF.