NF-κB mediates IL-1β-induced synthesis/release of α₂-macroglobulin in a human glial cell line

Increasingly, inflammatory responses in localized areas of brain parenchyma in response to the extracellular deposition of the Aβ peptides are thought to play a causative role in Alzheimer's disease (AD) progression. Anti-inflammatory agents, in particular non-steroid anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, have been shown to be associated with a delayed onset or slowed rate of disease progression in several epidemiological studies. Activation of glial cells and the subsequent expression of a number of proteins including α₂-macroglobulin (α₂M) are associated with the induction of brain tissue inflammation. Additionally cytokines, such as interleukin-1α (IL-1α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) are co-localized to senile plaques, a neuropathological hallmark of AD. α₂M binds various cytokines, including IL-1β, as well as Aβ. In this study, we demonstrate that IL-1β induces α₂M synthesis/release from a human astroglial cell line (U373) via the activation of the nuclear transcription factor NF-κB. Our data suggest that attenuation of IL-1β-induced α₂M synthesis/release by blocking NF-κB activation may potentially be 'protective' against the development of late-onset AD.