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

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.