BiP/GRP78-induced production of cytokines and uptake of amyloid-beta(1-42)peptide in microglia

Citation
J. Kakimura et al., BiP/GRP78-induced production of cytokines and uptake of amyloid-beta(1-42)peptide in microglia, BIOC BIOP R, 281(1), 2001, pp. 6-10
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
281
Issue
1
Year of publication
2001
Pages
6 - 10
Database
ISI
SICI code
0006-291X(20010216)281:1<6:BPOCAU>2.0.ZU;2-4
Abstract
In the brains of Alzheimer's disease (AD) patients, fibrillar amyloid-beta peptides (A beta) are markedly accumulated and the microglia associate with the amyloid plaques, However, the regulation of A P clearance is still unc lear. In the present study, we examined the effect of a chaperone protein B iP/GRP78 on the microglial function. Exogenous addition of recombinant BiP/ GRP78 induced the production of cytokines such as interleukin-6 and tumor n ecrosis factor-alpha, but heat treatment of this protein abolished the acti vity. Although A beta (1-42) did not induce cytokine production, it was tak en up by the microglia. In addition, the amount of A beta (1-42) uptake and the number of microglia that phagocytosed A beta (1-42) were markedly incr eased by BiP/GRP78. Exogenous BiP/GRP78 also translocated to the endoplasmi c reticulum (ER). These results suggest that BiP/GRP78 stimulates A beta cl earance in the microglia, and that dysfunction in the ER may cause the accu mulation of extracellular A beta (1-42). (C) 2001 Academic Press.