Interleukin-1beta up-regulates TACE to enhance alpha-cleavage of APP in neurons: resulting decrease in Abeta production.

Interleukin-1beta up-regulates TACE to enhance alpha-cleavage of APP in neurons: resulting decrease in Abeta production. Research Abstract Details 

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Interleukin-1beta up-regulates TACE to enhance alpha-cleavage of APP in neurons: resulting decrease in Abeta production. Abstract Text:

Yuriko Tachida,Kazuhiro Nakagawa,Takashi Saito,Takaomi C Saido,Takashi Honda,Yuko Saito,Shigeo Murayama,Tamao Endo,Gaku Sakaguchi,Akira Kato,Shinobu Kitazume,Yasuhiro Hashimoto,

The proinflammatory cytokine interleukin (IL)-1beta is up-regulated in microglial cells surrounding amyloid plaques, leading to the hypothesis that IL-1beta is a risk factor for Alzheimer's disease. However, we unexpectedly found that IL-1beta significantly enhanced alpha-cleavage, indicated by increases in sAPPalpha and C83, but reduced beta-cleavage, indicated by decreases in sAPPbeta and Abeta40/42, in human neuroblastoma SK-N-SH cells. IL-1beta did not significantly alter the mRNA levels of BACE1, ADAM-9, and ADAM-10, but up-regulated that of TACE by threefold. The proform and mature form of TACE protein were also significantly up-regulated. A TACE inhibitor (TAPI-2) concomitantly reversed the IL-1beta-dependent increase in sAPPalpha and decrease in sAPPbeta, suggesting that APP consumption in the alpha-cleavage pathway reduced its consumption in the beta-cleavage pathway. IL-1Ra, a physiological antagonist for the IL-1 receptor, reversed the effects of IL-1beta, suggesting that the IL-1beta-dependent up-regulation of alpha-cleavage is mediated by the IL-1 receptor. IL-1beta also induced this concomitant increase in alpha-cleavage and decrease in beta-cleavage in mouse primary cultured neurons. Taken together we conclude that IL-1beta is an anti-amyloidogenic factor, and that enhancement of its signaling or inhibition of IL-1Ra activity could represent potential therapeutic strategies against Alzheimer's disease.

Interleukin-1beta up-regulates TACE to enhance alpha-cleavage of APP in neurons: resulting decrease in Abeta production. Publishing Authors By Initials

Y Tachida,K Nakagawa,T Saito,TC Saido,T Honda,Y Saito,S Murayama,T Endo,G Sakaguchi,A Kato,S Kitazume,Y Hashimoto,

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Interleukin-1beta up-regulates TACE to enhance alpha-cleavage of APP in neurons: resulting decrease in Abeta production. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of neurochemistry

VOLUME: 104

Page Numbers: 1387-93

Journal Abbreviation: J. Neurochem.

ISSN: 1471-4159

DAY: 16

MONTH: 11

YEAR: 2007

Interleukin-1beta up-regulates TACE to enhance alpha-cleavage of APP in neurons: resulting decrease in Abeta production. Information

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LANGUAGE: eng

NlmUniqueID: 2985190

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Grant and Affiliation Information for Interleukin-1beta up-regulates TACE to enhance alpha-cleavage of APP in neurons: resulting decrease in Abeta production.

AFFILIATION: Glyco-chain Functions Laboratory, Supra-biomolecular System Group, Frontier Research System, The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.

Country: England

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MEDLINETA: J Neurochem

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