Effect of a carboxy-terminal fragment of the Alzheimer's amyloid precursor protein on expression of proinflammatory cytokines in rat glial cells.
To explore factors involved in the induction of cytokines that may contribute to the pathogenesis of Alzheimer's disease (AD), the effect of a carboxy terminal 105 amino acid fragment (CT105) of the amyloid precursor protein (APP) on the gene expression of proinflammatory cytokines, IL-1beta and IL-6 was determined in cultured rat cortical glial cells in comparision to amyloid beta protein (A beta). Cells were incubated with 1 microM of insoluble CT105 aggregates or aged A beta1-40 peptide deposits which were mainly composed of stable monomeric and dimeric forms as assessed on Western blots. The levels of mRNAs were analyzed by reverse transcription polymerase chain reaction (RT-PCR). Highest levels of both IL-1beta and IL-6 transcripts were detected in the culture exposed to CT105 aggregates for 4 days. CT105 aggregates markedly increased IL-1beta mRNA level by 3.5 fold of the control level and this effect was more potent than that produced by aged A beta1-40 peptides. Furthermore, CT105 strongly induced accumulation of IL-6 mRNA level by 2 fold of the value potentiated by A beta1-40. Such induction was not observed with A beta 12-28 treatment. On the other hand, CT105 did not significantly alter either APP or glial fibrillary acidic protein (GFAP) mRNA levels. These results together imply that CT peptide besides its cytotoxic potency may act as a potent immunological component, strongly inducing both IL-1beta and IL-6 mRNA levels in the cultured glial cells. This CT peptide associated exacerbation of cytokine expression may be in part responsible for chronic inflammation linked to slowly progressive neurodegeneration characteristic to AD.
Chong
Y
Y
Department of Microbiology, College of Medicine, Medical Science Research Center, Ewha Womans University, Seoul, Korea. younghae@mm.ewha.ac.kr
D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1; D015850:Interleukin-6; D010446:Peptide Fragments; D012333:RNA, Messenger