Differential suppression of endotoxin-inducible inflammatory cytokines by nuclear factor kappa B (NFκB) inhibitor in rat microglia

Abstract The molecular mechanism by which the deleterious cytokines interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) are induced in endotoxin-stimulated microglia was investigated from the viewpoint of signal transduction. Neither cytokine is produced in nonstimulated rat microglia, but both are remarkably induced by stimulation with endotoxin lipopolysaccharide (LPS). LPS-inducible IL-1β was significantly suppressed by pretreatment with the nuclear factor kappa B (NFκB) inhibitor ammonium pyrrolidine dithiocarbamate (APDC), but TNFα was not. APDC was actually confirmed to suppress the degradation of IκBα and IκBβ in microglia, indicating a role for the inhibitor of NFκB activation. Taken together, these results suggest that the induction of IL-1β and TNFα in endotoxin-stimulated microglia is differentially regulated at the level of NFκB activation.