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Effects of the β-Amyloid and Carboxyl-terminal Fragment of Alzheimer's Amyloid Precursor Protein on the Production of the Tumor Necrosis Factor-α and Matrix Metalloproteinase-9 by Human Monocytic THP-1

Title
Effects of the β-Amyloid and Carboxyl-terminal Fragment of Alzheimer's Amyloid Precursor Protein on the Production of the Tumor Necrosis Factor-α and Matrix Metalloproteinase-9 by Human Monocytic THP-1
Authors
Chong Y.H.Sung J.H.Shin S.A.Chung J.-H.Suh Y.-H.
Ewha Authors
정영해
SCOPUS Author ID
정영해scopus
Issue Date
2001
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 276, no. 26, pp. 23511 - 23517
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
To explore the direct role of β-amyloid (Aβ) and carboxyl-terminal fragments of amyloid precursor protein in the inflammatory processes possibly linked to neurodegeneration associated with Alzheimer's disease, the effects of the 105-amino acid carboxyl-terminal fragment (CT 105) of amyloid precursor protein on the production of tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) were examined in a human monocytic THP-1 cell line and compared with that of Aβ. CT 105 elicited a marked increase in TNF-α and MMP-9 production in the presence of interferon-γ in a dose- and time-dependent manner. Similar patterns were obtained with Aβ despite its low magnitude of induction. Autocrine TNF-α is likely to be a main mediator of the induction of MMP-9 because the neutralizing antibody to TNF-α inhibits MMP-9 production. Genistein, a specific inhibitor of tyrosine kinase, dramatically diminished both TNF-α secretion and subsequent MMP-9 release in response to CT 105 or Aβ. Furthermore, PD98059 and SB202190, specific inhibitors of ERK or p38 MAPK respectively, efficiently suppressed CT 105-induced effects whereas only PD98059 was effective at reducing Aβ-induced effects. Our results suggest that CT 105 in combination with interferon-γ might serve as a more potent activator than Aβ in triggering inflammatory processes and that both tyrosine kinase and MAPK signaling pathways may represent potential therapeutic targets for the control of Alzheimer's disease progression.
DOI
10.1074/jbc.M009466200
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의학전문대학원 > 의학과 > Journal papers
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