APOLIPOPROTEIN-E SUPPRESSES GLIAL-CELL SECRETION OF TNF-ALPHA

Apolipoprotein E (apoE) is a 299 amino acid protein with multiple biol ogical functions. Initially described in the context of cholesterol me tabolism, apoE also has immunomodulatory properties and recent evidenc e has implicated a role for apoE in neurological disease. One possibil ity is that apoE, which is the predominant apolipoprotein produced int ra-axially, may modify the CNS response to acute and chronic injury. W e prepared mixed neuronal-glial cultures from apoE deficient mouse pup s and measured secretion of TNF alpha after stimulation with lipopolys accharide (LPS) in the presence and absence of human recombinant apoE3 and E4. We demonstrate that preincubation with apoE blocks glial secr etion of TNF alpha in a dose-dependent manner. This effect is independ ent of any direct effect of apoE on cell viability and is greatest whe n apoE is preincubated with the cell culture for 24 h.