title: NF-kappaB mediates IL-1beta-induced synthesis/release of alpha2-macroglobulin in a human glial cell line.
abstract: Increasingly, inflammatory responses in localized areas of brain parenchyma in response to the extracellular deposition of the Abeta 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 alpha(2)-macroglobulin (alpha(2)M) are associated with the induction of brain tissue inflammation. Additionally cytokines, such as interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) are co-localized to senile plaques, a neuropathological hallmark of AD. Alpha(2)M binds various cytokines, including IL-1beta, as well as Abeta. In this study, we demonstrate that IL-1beta induces alpha(2)M synthesis/release from a human astroglial cell line (U373) via the activation of the nuclear transcription factor NF-kappaB. Our data suggest that attenuation of IL-1beta-induced alpha(2)M synthesis/release by blocking NF-kappaB activation may potentially be 'protective' against the development of late-onset AD.
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46285, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Bales
authors.forename: Richard C
authors.initials: RC
authors.lastname: Dodel
authors.forename: Junyi
authors.initials: J
authors.lastname: Liu
authors.forename: Xianming
authors.initials: X
authors.lastname: Chen
authors.forename: Harald
authors.initials: H
authors.lastname: Hample
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.forename: Steven M
authors.initials: SM
authors.lastname: Paul
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D004660:Encephalitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D000511:alpha-Macroglobulins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D000511:alpha-Macroglobulins