NF-kappaB mediates IL-1beta-induced synthesis/release of alpha2-macroglobulin in a human glial cell line.
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.
Gao
Feng
F
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46285, USA.
Bales
Kelly R
KR
Dodel
Richard C
RC
Liu
Junyi
J
Chen
Xianming
X
Hample
Harald
H
Farlow
Martin R
MR
Paul
Steven M
SM
Du
Yansheng
Y
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
D007375:Interleukin-1; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D000511:alpha-Macroglobulins